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1.
Clin Sci (Lond) ; 136(1): 121-137, 2022 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-34821367

RESUMO

Chemokine (C-C motif) ligand 5 (CCL5) and CCR5, one of its receptors have been reported to be highly expressed in white adipose tissue (WAT) and are associated with the progression of inflammation and the development of insulin resistance in obese humans and mice. However, the role of CCL5/CCR5 signaling in obesity-associated dysregulation of energy metabolism remains unclear. Here, we demonstrate that global CCL5/CCR5 double knockout (DKO) mice have higher cold stress-induced energy expenditure and thermogenic function in brown adipose tissue (BAT) than wildtype (WT) mice. DKO mice have higher cold stress-induced energy expenditure and thermogenic function in BAT than WT mice. KEGG pathway analysis indicated that deletion of CCL5/CCR5 further facilitated the cold-induced expression of genes related to oxidative phosphorylation (OxPhos) and lipid metabolic pathways. In primary brown adipocytes of DKO mice, the augmentation of CL-316243-stimulated thermogenic and lipolysis responses was reversed by co-treatment with AMPKα1 and α2 short interfering RNA (siRNA). Overexpression of BAT CCL5/CCR5 genes by local lentivirus injection in WT mice suppressed cold stress-induced lipolytic processes and thermogenic activities. In contrast, knockdown of BAT CCL5/CCR5 signaling further up-regulated AMPK phosphorylation as well as thermogenic and lipolysis responses to chronic adrenergic stimuli and subsequently decreased level of body weight gain. Chronic knockdown of BAT CCL5/CCR5 signaling improved high-fat diet (HFD)-induced insulin resistance in WT mice. It is suggested that obesity-induced augmentation of adipose tissue (AT) CCL5/CCR5 signaling could, at least in part, suppress energy expenditure and adaptive thermogenesis by inhibiting AMPK-mediated lipolysis and oxidative metabolism in thermogenic AT to exacerbate the development of obesity and insulin resistance.


Assuntos
Tecido Adiposo Marrom/metabolismo , Quimiocina CCL5/metabolismo , Resistência à Insulina , Obesidade/metabolismo , Receptores CCR5/metabolismo , Animais , Quimiocina CCL5/genética , Dieta Hiperlipídica , Regulação da Expressão Gênica , Camundongos , Camundongos Knockout , Fosforilação Oxidativa , Receptores CCR5/genética , Transdução de Sinais , Termogênese
2.
Int J Mol Sci ; 23(16)2022 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-36012714

RESUMO

Brown adipose tissue (BAT) has been considered a vital organ in response to non-shivering adaptive thermogenesis, which could be activated during cold exposure through the sympathetic nervous system (SNS) or under postprandial conditions contributing to diet-induced thermogenesis (DIT). Humans prefer to live within their thermal comfort or neutral zone with minimal energy expenditure created by wearing clothing, making shelters, or using an air conditioner to regulate their ambient temperature; thereby, DIT would become an important mechanism to counter-regulate energy intake and lipid accumulation. In addition, there has been a long interest in the intriguing possibility that a defect in DIT predisposes one to obesity and other metabolic diseases. Due to the recent advances in methodology to evaluate the functional activity of BAT and DIT, this updated review will focus on the role and regulatory mechanism of BAT biology in DIT in health and diseases and whether these mechanisms are applicable to humans.


Assuntos
Tecido Adiposo Marrom , Termogênese , Tecido Adiposo Marrom/metabolismo , Temperatura Baixa , Ingestão de Energia/fisiologia , Metabolismo Energético/fisiologia , Humanos , Obesidade/metabolismo , Termogênese/fisiologia
3.
Int J Mol Sci ; 23(22)2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36430701

RESUMO

The C-C chemokine motif ligand 5 (CCL5) and its receptors have recently been thought to be substantially involved in the development of obesity-associated adipose tissue inflammation and insulin resistance. However, the respective contributions of tissue-derived and myeloid-derived CCL5 to the etiology of obesity-induced adipose tissue inflammation and insulin resistance, and the involvement of monocytic myeloid-derived suppressor cells (MDSCs), remain unclear. This study used CCL5-knockout mice combined with bone marrow transplantation (BMT) and mice with local injections of shCCL5/shCCR5 or CCL5/CCR5 lentivirus into bilateral epididymal white adipose tissue (eWAT). CCL5 gene deletion significantly ameliorated HFD-induced inflammatory reactions in eWAT and protected against the development of obesity and insulin resistance. In addition, tissue (non-hematopoietic) deletion of CCL5 using the BMT method not only ameliorated adipose tissue inflammation by suppressing pro-inflammatory M-MDSC (CD11b+Ly6G-Ly6Chi) accumulation and skewing local M1 macrophage polarization, but also recruited reparative M-MDSCs (CD11b+Ly6G-Ly6Clow) and M2 macrophages to the eWAT of HFD-induced obese mice, as shown by flow cytometry. Furthermore, modulation of tissue-derived CCL5/CCR5 expression by local injection of shCCL5/shCCR5 or CCL5/CCR5 lentivirus substantially impacted the distribution of pro-inflammatory and reparative M-MDSCs as well as macrophage polarization in bilateral eWAT. These findings suggest that an obesity-induced increase in adipose tissue CCL5-mediated signaling is crucial in the recruitment of tissue M-MDSCs and their trans-differentiation to tissue pro-inflammatory macrophages, resulting in adipose tissue inflammation and insulin resistance.


Assuntos
Tecido Adiposo , Quimiocina CCL5 , Inflamação , Células Supressoras Mieloides , Receptores CCR5 , Animais , Camundongos , Tecido Adiposo/química , Tecido Adiposo/metabolismo , Dieta Hiperlipídica/efeitos adversos , Inflamação/metabolismo , Resistência à Insulina/genética , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Obesos , Células Supressoras Mieloides/metabolismo , Obesidade/metabolismo , Receptores CCR5/genética , Receptores CCR5/metabolismo , Quimiocina CCL5/metabolismo , Quimiocina CCL5/farmacologia
4.
Int J Mol Sci ; 22(24)2021 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-34948325

RESUMO

Obesity is characterized as a complex and multifactorial excess accretion of adipose tissue accompanied with alterations in the immune and metabolic responses. Although the chemokine systems have been documented to be involved in the control of tissue inflammation and metabolism, the dual role of chemokines and chemokine receptors in the pathogenesis of the inflammatory milieu and dysregulated energy metabolism in obesity remains elusive. The objective of this review is to present an update on the link between chemokines and obesity-related inflammation and metabolism dysregulation under the light of recent knowledge, which may present important therapeutic targets that could control obesity-associated immune and metabolic disorders and chronic complications in the near future. In addition, the cellular and molecular mechanisms of chemokines and chemokine receptors including the potential effect of post-translational modification of chemokines in the regulation of inflammation and energy metabolism will be discussed in this review.


Assuntos
Quimiocinas/metabolismo , Metabolismo Energético/fisiologia , Inflamação/metabolismo , Obesidade/metabolismo , Animais , Humanos , Inflamação/patologia , Obesidade/patologia , Processamento de Proteína Pós-Traducional/fisiologia
5.
Int J Mol Sci ; 20(13)2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31247902

RESUMO

Obesity and insulin resistance are two major risk factors for the development of metabolic syndrome, type 2 diabetes and associated cardiovascular diseases (CVDs). Cyclooxygenase (COX), a rate-limiting enzyme responsible for the biosynthesis of prostaglandins (PGs), exists in two isoforms: COX-1, the constitutive form, and COX-2, mainly the inducible form. COX-2 is the key enzyme in eicosanoid metabolism that converts eicosanoids into a number of PGs, including PGD2, PGE2, PGF2α, and prostacyclin (PGI2), all of which exert diverse hormone-like effects via autocrine or paracrine mechanisms. The COX-2 gene and immunoreactive proteins have been documented to be highly expressed and elevated in adipose tissue (AT) under morbid obesity conditions. On the other hand, the environmental stress-induced expression and constitutive over-expression of COX-2 have been reported to play distinctive roles under different pathological and physiological conditions; i.e., over-expression of the COX-2 gene in white AT (WAT) has been shown to induce de novo brown AT (BAT) recruitment in WAT and then facilitate systemic energy expenditure to protect mice against high-fat diet-induced obesity. Hepatic COX-2 expression was found to protect against diet-induced steatosis, obesity, and insulin resistance. However, COX-2 activation in the epidydimal AT is strongly correlated with the development of AT inflammation, insulin resistance, and fatty liver in high-fat-diet-induced obese rats. This review will provide updated information regarding the role of COX-2-derived signals in the regulation of energy metabolism and the pathogenesis of obesity and MS.


Assuntos
Ciclo-Oxigenase 2/metabolismo , Resistência à Insulina , Obesidade/metabolismo , Transdução de Sinais , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Animais , Biomarcadores , Metabolismo Energético , Humanos , Fígado/metabolismo , Fígado/patologia , Modelos Biológicos , Terapia de Alvo Molecular , Obesidade/complicações , Obesidade/tratamento farmacológico , Prostaglandinas/metabolismo
6.
Clin Sci (Lond) ; 132(14): 1581-1596, 2018 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-29773671

RESUMO

Adipose tissue (AT) inflammation is crucial to the development of obesity-associated insulin resistance. Our aim was to investigate the contribution of cyclooxygenase-2 (COX-2)/macrophage migration inhibitory factor (MIF)-mediated cross-talk between hypertrophic adipocytes and macrophages to the etiology of AT inflammation and the involvement of CD74 using human SGBS adipocytes, THP-1 macrophages and mice fed a high-fat (HF) diet. The MIF and CD74 mRNA levels in the adipocytes and stromal vascular cells (SVCs) of white fat were highly correlated with body weight (BW), homeostatic model assessment for insulin resistance (HOMA-IR), and adipose macrophage marker expression levels, especially those in SVCs. COX-2 inhibition suppressed the elevation of MIF production in HF white adipocytes as well as palmitate and hypoxic-treated SGBS adipocytes. Treatment of adipocytes transfected with shCOX-2 and siMIF or subjected to MIF depletion in the medium reversed the pro-inflammatory responses in co-incubated THP-1 cells. Inhibition of NF-κB activation reversed the COX2-dependent MIF secretion from treated adipocytes. The targetted inhibition of macrophage CD74 prevented M1 macrophage polarization in the above co-culture model. The COX-2-dependent increases in CD74 gene expression and MIF release in M1-polarized macrophages facilitated the expression of COX-2 and MIF in co-cultured SGBS adipocytes. CD74 shRNA intravenous injection suppressed HF-induced AT M1 macrophage polarization and inflammation as well as insulin resistance in mice. The present study suggested that COX-2-mediated MIF secretion through NF-κB activation from hypertrophic and hypoxic adipocytes as well as M1 macrophages might substantially contribute to the phenotypic switch of AT macrophages through CD74 in obesity. Inhibition of CD74 could attenuate AT inflammation and insulin resistance in the development of HF diet-induced obesity.


Assuntos
Adipócitos/metabolismo , Tecido Adiposo/metabolismo , Antígenos de Diferenciação de Linfócitos B/metabolismo , Ciclo-Oxigenase 2/metabolismo , Antígenos de Histocompatibilidade Classe II/metabolismo , Fatores Inibidores da Migração de Macrófagos/metabolismo , Macrófagos/metabolismo , Obesidade/metabolismo , Adipócitos/citologia , Tecido Adiposo/citologia , Animais , Antígenos de Diferenciação de Linfócitos B/genética , Células Cultivadas , Dieta Hiperlipídica/efeitos adversos , Antígenos de Histocompatibilidade Classe II/genética , Humanos , Inflamação/genética , Inflamação/metabolismo , Resistência à Insulina/genética , Ativação de Macrófagos , Fatores Inibidores da Migração de Macrófagos/genética , Macrófagos/classificação , Masculino , Camundongos Endogâmicos C57BL , Obesidade/etiologia , Obesidade/genética , Interferência de RNA , Células THP-1
7.
Chin J Physiol ; 61(5): 266-279, 2018 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-30384400

RESUMO

Regulated upon activation, normal T cell expressed, and secreted (RANTES), also known as chemokine ligand 5 (CCL5), has been reported to facilitate macrophage migration, which plays a crucial role in tissue inflammation. The aim of this study is to investigate the characteristics and underlying mechanism of RANTES on macrophage chemotaxis under physiological and pathological conditions. The study was conducted on macrophage RAW264.7 cell and bone marrow-derived macrophages (BMDM) isolated from CCL receptor 5 (CCR5) knockout mice. The macrophage migration and glucose uptake was assessed in time and dose dependent manners. Moreover, reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis were used to characterize mRNA and protein level related to the underlying mechanism. The present result showed that the maraviroc, a selective CCR5 inhibitor, dose-dependently suppressed RANTES-induced rapid increases in glucose uptake and cell migration in RAW264.7 cells. Similar effects were observed in the BMDM isolated from CCR5 knockout mice compared with wild type control. RANTES treatment promptly enhanced membrane glucose transporter 1 (GLUT1) expression, glucose uptake as well as phosphorylation of AKT on Thr308, Ser473 within min and has prolonged effect on phosphorylation of AMP-activated protein kinase (AMPK) on Thr172, which were abrogated by maraviroc, CCR5 siRNA or phospholipase C (PLC) inhibitor in RAW264.7 cells. Inhibition of PI3K and AMPK by LY294002 and Compound C significantly suppress RANTES-stimulated macrophage glucose uptake and migration, respectively. RANTES has biphasic effect on activating PLC signaling including prompt action on PI3K/AKT phosphorylation and prolong action on AMPK phosphorylation via CCR5 which leads to increased GLUT1-mediated glucose uptake and macrophage migration under physiopathological states.


Assuntos
Quimiocina CCL5 , Macrófagos , Animais , Quimiotaxia , Camundongos , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Receptores CCR5 , Transdução de Sinais , Linfócitos T , Fosfolipases Tipo C
8.
FASEB J ; 30(6): 2282-97, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26932930

RESUMO

We examined the involvement of adipocyte cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2)-prostaglandin E receptor (EP)3-mediated signaling during hypertrophy and hypoxia in the development of obesity-associated adipose tissue (AT) inflammation and insulin resistance. The experiments were conducted with high-fat diet (HFD)-induced obese rats, db/db mice, human subjects, and 3T3-L1 and the human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes; the groups were treated with selective inhibitors of COX-2 [celecoxib 30 mg/kg, half maximal inhibitory concentration (IC50) ≈ 0.04 µM] and EP3 (L-798106 100 µg/kg, IC50 ≈ 0.5 µM) or a short interfering RNA. There were strong, positive correlations between adipocyte COX-2 and EP3 gene expressions and the AT TNF-α and monocyte chemotactic protein-1 contents and the homeostatic model assessment for insulin resistance in HFD-induced obese rats, as well as body mass index in human subjects. Treatment with COX-2 and EP3 inhibitors significantly reversed AT inflammatory gene and protein expressions (-50%) and impaired glucose and insulin tolerance in db/db mice. COX-2 inhibition diminished the chemotaxis of adipocytes isolated from HFD rats to macrophages and T cells. Targeting inhibition of adipocyte COX-2 and EP3 during hypertrophy and hypoxia reversed the release of the augmented proinflammatory adipokines and the diminished adiponectin and also suppressed NF-κB and hypoxia-inducible factor-1α transcription activation. These findings suggest that adipocyte COX-2 PGE2-EP3-mediated signaling is crucially involved in the development of obesity-associated AT inflammation and insulin resistance.-Chan, P.-C., Hsiao, F.-C., Chang, H.-M., Wabitsch, M., Hsieh, P. S. Importance of adipocyte cyclooxygenase-2 and prostaglandin E2-prostaglandin E receptor 3 signaling in the development of obesity-induced adipose tissue inflammation and insulin resistance.


Assuntos
Adipócitos/enzimologia , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Resistência à Insulina/fisiologia , Obesidade/patologia , Receptores de Prostaglandina E Subtipo EP3/metabolismo , Células 3T3-L1 , Adipócitos/metabolismo , Animais , Ciclo-Oxigenase 2/genética , Dinoprostona/genética , Inflamação/etiologia , Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos NOD , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Receptores de Prostaglandina E Subtipo EP3/genética , Transdução de Sinais/fisiologia
9.
Eur J Pharmacol ; 891: 173703, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33159935

RESUMO

Obesity is closely linked with type 2 diabetes and the effective therapies on obesity-associated diabetes are under development. The aim of this study was undertaken to investigate whether the inhibition of the augmented CCR5-mediated signaling could be a common target for treatment of obesity-associated insulin resistance and impairment of pancreatic insulin secretion in high-fat diet (HFD) fed rats and CCR5 knockout mice and also in isolated islets and RIN-m5F cells. Conducted with SD rats, HFD-induced body weight gain was significantly decreased in those combined with Maraviroc treatment, but food intake remained similar compared to control. Maraviroc also significantly improved the impaired oral glucose tolerance test (OGTT). As compared with wild-type mice, CCR5 deletion significantly attenuated the HFD-induced increases in glucose area under curve of OGTT and the value of HOMA-IR as well as plasma lipid profile. It also reversed the HFD-suppressed gene expressions of GLUT4 and IRS-1 in adipose tissue. On the other hand, the HFD-associated islet macrophage and T-cell infiltration were significantly decreased in CCR5 KO mice. H2O2 significantly suppressed glucose-stimulated insulin secretion (GSIS) is isolated islets, which were significantly reversed in those cotreated with CCR5 mAb. H2O2 failed to change GSIS in those of CCR5 KO mice. The palmitate-induced reactive oxygen species production was significantly decreased in those cotreated with CCR5 antagonist in RIN-m5F cells. Collectively, it is suggested that targeting inhibition of the CCR5 mediated inflammatory pathway could not only improve obesity-associated insulin resistance but also directly alleviate pancreatic ß-cell dysfunction.


Assuntos
Glicemia/efeitos dos fármacos , Antagonistas dos Receptores CCR5/farmacologia , Resistência à Insulina , Células Secretoras de Insulina/efeitos dos fármacos , Insulina/metabolismo , Maraviroc/farmacologia , Obesidade/prevenção & controle , Receptores CCR5/efeitos dos fármacos , Animais , Glicemia/metabolismo , Linhagem Celular Tumoral , Dieta Hiperlipídica , Modelos Animais de Doenças , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Obesidade/complicações , Obesidade/metabolismo , Obesidade/fisiopatologia , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Receptores CCR5/genética , Receptores CCR5/metabolismo , Via Secretória , Transdução de Sinais , Técnicas de Cultura de Tecidos
10.
Free Radic Biol Med ; 112: 200-211, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28778482

RESUMO

Elevations in C-reactive protein (CRP) levels are positively correlated with the progress of type 2 diabetes mellitus. However, the effect of CRP on pancreatic insulin secretion is unknown. Here, we showed that purified human CRP impaired insulin secretion in isolated mouse islets and NIT-1 insulin-secreting cells in dose- and time-dependent manners. CRP increased NADPH oxidase-mediated ROS (reactive oxygen species) production, which simultaneously promoted the production of nitrotyrosine (an indicator of RNS, reactive nitrogen species) and TNFα, to diminish cell viability, insulin secretion in islets and insulin-secreting cells. These CRP-mediated detrimental effects on cell viability and insulin secretion were significantly reversed by adding NAC (a potent antioxidant), apocynin (a selective NADPH oxidase inhibitor), L-NAME (a non-selective nitric oxide synthase (NOS) inhibitor), aminoguanidine (a selective iNOS inhibitor), PDTC (a selective NFκB inhibitor) or Enbrel (an anti-TNFα fusion protein). However, CRP-induced ROS production failed to change after adding L-NAME, aminoguanidine or PDTC. In isolated islets and NIT-1 cells, the elevated nitrotyrosine contents by CRP pretreatment were significantly suppressed by adding L-NAME but not PDTC. Conversely, CRP-induced increases in TNF-α production were significantly reversed by administration of PDTC but not L-NAME. In addition, wild-type mice treated with purified human CRP showed significant decreases in the insulin secretion index (HOMA-ß cells) and the insulin stimulation index in isolated islets that were reversed by the addition of L-NAME, aminoguanidine or NAC. It is suggested that CRP-activated NADPH-oxidase redox signaling triggers iNOS-mediated RNS and NFκB-mediated proinflammatory cytokine production to cause ß cell damage in state of inflammation.


Assuntos
Proteína C-Reativa/farmacologia , Células Secretoras de Insulina/efeitos dos fármacos , Insulina/metabolismo , NADPH Oxidases/genética , Transdução de Sinais , Acetofenonas/farmacologia , Acetilcisteína/farmacologia , Animais , Linhagem Celular , Relação Dose-Resposta a Droga , Etanercepte/farmacologia , Regulação da Expressão Gênica , Guanidinas/farmacologia , Humanos , Secreção de Insulina , Células Secretoras de Insulina/citologia , Células Secretoras de Insulina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , NADPH Oxidases/antagonistas & inibidores , NADPH Oxidases/metabolismo , NF-kappa B/antagonistas & inibidores , NF-kappa B/genética , NF-kappa B/metabolismo , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Oxirredução , Prolina/análogos & derivados , Prolina/farmacologia , Espécies Reativas de Nitrogênio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Tiocarbamatos/farmacologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Tirosina/análogos & derivados , Tirosina/metabolismo
11.
Obesity (Silver Spring) ; 17(6): 1150-7, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19247274

RESUMO

The aim was to examine the role of cyclooxygenase (COX)-2-mediated inflammation in the development of obese linked insulin resistance and fatty liver. The rats were fed separately regular diet (CONT), high-fat diet (HFD) ad libitum, or energy restrictedly for 12 weeks. Rats fed HFD ad libitum were further divided into three subgroups co-treated with vehicle (HFa), or a selective COX-2 inhibitor celecoxib (HFa-Cel) or mesulid (HFa-Mes). Euglycemic hyperinsulinemic clamp (EHC) experiment was performed at the end of study. Another set of rats with similar grouping was further divided into those with a 4, 8, or 12-week intervention period for hepatic sampling. Body weight was increased significantly and similarly in HFa, HFa-Cel, and HFa-Mes. Time-dependent increases in plasma insulin, glucose, 8-isoprostanes, leptin levels, homeostasis model assessment of insulin resistance (HOMA-IR) and hepatic triglyceride contents shown in HFa were significantly reversed in HFa-Cel and HFa-Mes. During EHC period, the reduction in stimulation of whole body glucose uptake, suppression of hepatic glucose production and metabolic clearance rate of insulin shown in HFa were significantly reversed in HFa-Cel and HFa-Mes. The enhanced COX-2 and tumor necrosis factor-alpha (TNF-alpha) but attenuated PPAR-gamma and C/EBP-alpha mRNA expressions in epididymal fat shown in HFa were significantly reversed in HFa-Cel and HFa-Mes. The increases in average cell size of adipocytes and CD68 positive cells shown in HFa were also significantly reversed in HFa-Cel and HFa-Mes. Our findings suggest that COX-2 activation in fat inflammation is important in the development of insulin resistance and fatty liver in high fat induced obese rats.


Assuntos
Adipócitos/enzimologia , Tecido Adiposo/enzimologia , Ciclo-Oxigenase 2/metabolismo , Fígado Gorduroso/etiologia , Resistência à Insulina , Obesidade/complicações , Paniculite/etiologia , Adipócitos/efeitos dos fármacos , Adipócitos/patologia , Adipogenia , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/patologia , Animais , Glicemia/metabolismo , Peso Corporal , Celecoxib , Tamanho Celular , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/genética , Inibidores de Ciclo-Oxigenase 2/farmacologia , Dinoprosta/análogos & derivados , Dinoprosta/sangue , Modelos Animais de Doenças , Fígado Gorduroso/enzimologia , Fígado Gorduroso/patologia , Insulina/sangue , Leptina/sangue , Fígado/metabolismo , Fígado/patologia , Macrófagos/metabolismo , Masculino , Proteínas de Membrana/metabolismo , Obesidade/enzimologia , Obesidade/patologia , Paniculite/enzimologia , Paniculite/patologia , Pirazóis/farmacologia , Ratos , Ratos Sprague-Dawley , Sulfonamidas/farmacologia , Fatores de Tempo , Triglicerídeos/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
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