RESUMO
Obesity-associated inflammation in white adipose tissue (WAT) is a causal factor of systemic insulin resistance; however, precisely how immune cells regulate WAT inflammation in relation to systemic insulin resistance remains to be elucidated. The present study examined a role for 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) in hematopoietic cells in regulating WAT inflammation and systemic insulin sensitivity. Male C57BL/6J mice were fed a high-fat diet (HFD) or low-fat diet (LFD) for 12 weeks and examined for WAT inducible 6-phosphofructo-2-kinase (iPFK2) content, while additional HFD-fed mice were treated with rosiglitazone and examined for PFKFB3 mRNAs in WAT stromal vascular cells (SVC). Also, chimeric mice in which PFKFB3 was disrupted only in hematopoietic cells and control chimeric mice were also fed an HFD and examined for HFD-induced WAT inflammation and systemic insulin resistance. In vitro, adipocytes were co-cultured with bone marrow-derived macrophages and examined for adipocyte proinflammatory responses and insulin signaling. Compared with their respective levels in controls, WAT iPFK2 amount in HFD-fed mice and WAT SVC PFKFB3 mRNAs in rosiglitazone-treated mice were significantly increased. When the inflammatory responses were analyzed, peritoneal macrophages from PFKFB3-disrputed mice revealed increased proinflammatory activation and decreased anti-inflammatory activation compared with control macrophages. At the whole animal level, hematopoietic cell-specific PFKFB3 disruption enhanced the effects of HFD feeding on promoting WAT inflammation, impairing WAT insulin signaling, and increasing systemic insulin resistance. In vitro, adipocytes co-cultured with PFKFB3-disrupted macrophages revealed increased proinflammatory responses and decreased insulin signaling compared with adipocytes co-cultured with control macrophages. These results suggest that PFKFB3 disruption in hematopoietic cells only exacerbates HFD-induced WAT inflammation and systemic insulin resistance.
Assuntos
Tecido Adiposo Branco/metabolismo , Inflamação/metabolismo , Resistência à Insulina/fisiologia , Obesidade/metabolismo , Fosfofrutoquinase-2/metabolismo , Adipócitos/citologia , Adipócitos/metabolismo , Tecido Adiposo Branco/citologia , Animais , Células Cultivadas , Dieta com Restrição de Gorduras , Dieta Hiperlipídica , Modelos Animais de Doenças , Macrófagos/citologia , Macrófagos/metabolismo , Camundongos , Transdução de SinaisRESUMO
OBJECTIVE: To evaluate the clinical characteristics of patients with adrenocorticotropin-independent macronodular adrenal hyperplasia (AIMAH). METHODS: A total of 10 AIMAH cases were enrolled in this retrospective study. The clinical and laboratory findings of all patients were collected and analyzed. RESULTS: All patients manifested some clinical features and biochemical evidence of Cushing's syndrome. The plasma adrenocorticotropic hormone (ACTH) level was undetectable in all the patients and their serum cortisol secretion rhythm was abnormal. Low and high-dose dexamethasone suppression tests failed to suppress the cortisol secretion. The bilateral macronodular adrenal enlargement was shown by CT/magnetic resonance imaging. The supine-upright posture test was positive in four patients. Three patients were performed bilateral adrenalectomy, five were unilateral adrenalectomy and the remaining two patients were taken propranolol. All the patients had followed up for 10 to 89 months. Contralateral adrenalectomy was performed in two patients with recurrent symptoms after unilateral adrenalectomy and two patients given propranolol were underwent bilateral adrenalectomy when their symptoms had not been improved or recurred. CONCLUSION: AIMAH is a relatively rare subtype of Cushing's syndrome with unique clinical and laboratory findings. Propranolol is a good choice if the supine-upright posture test is positive. Unilateral adrenalectomy appears to be an effective and safe alternative treatment for AIMAH. Bilateral adrenalectomy could be performed if the symptoms have not been improved or recurred after unilateral adrenalectomy.
Assuntos
Hormônio Adrenocorticotrópico/sangue , Síndrome de Cushing , Adulto , Idoso , Síndrome de Cushing/tratamento farmacológico , Síndrome de Cushing/fisiopatologia , Síndrome de Cushing/cirurgia , Feminino , Humanos , Hidrocortisona/sangue , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Obesity-associated inflammation in white adipose tissue (WAT) is a causal factor of systemic insulin resistance. To better understand how adipocytes regulate WAT inflammation, the present study generated chimeric mice in which inducible 6-phosphofructo-2-kinase was low, normal, or high in WAT while the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (Pfkfb3) was normal in hematopoietic cells, and analyzed changes in high-fat diet (HFD)-induced WAT inflammation and systemic insulin resistance in the mice. Indicated by proinflammatory signaling and cytokine expression, the severity of HFD-induced WAT inflammation in WT â Pfkfb3+/- mice, whose Pfkfb3 was disrupted in WAT adipocytes but not hematopoietic cells, was comparable with that in WT â WT mice, whose Pfkfb3 was normal in all cells. In contrast, the severity of HFD-induced WAT inflammation in WT â Adi-Tg mice, whose Pfkfb3 was over-expressed in WAT adipocytes but not hematopoietic cells, remained much lower than that in WT â WT mice. Additionally, HFD-induced insulin resistance was correlated with the status of WAT inflammation and comparable between WT â Pfkfb3+/- mice and WT â WT mice, but was significantly lower in WT â Adi-Tg mice than in WT â WT mice. In vitro, palmitoleate decreased macrophage phosphorylation states of Jnk p46 and Nfkb p65 and potentiated the effect of interleukin 4 on suppressing macrophage proinflammatory activation. Taken together, these results suggest that the Pfkfb3 in adipocytes functions to suppress WAT inflammation. Moreover, the role played by adipocyte Pfkfb3 is attributable to, at least in part, palmitoleate promotion of macrophage anti-inflammatory activation.
Assuntos
Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Inflamação/metabolismo , Macrófagos/fisiologia , Fosfofrutoquinase-2/metabolismo , Adipócitos Brancos/metabolismo , Transferência Adotiva , Animais , Células Cultivadas , Citocinas/genética , Citocinas/metabolismo , Dieta Hiperlipídica/efeitos adversos , Gorduras na Dieta/administração & dosagem , Gorduras na Dieta/farmacologia , Ácidos Graxos Monoinsaturados/metabolismo , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Intolerância à Glucose , Resistência à Insulina , Masculino , Camundongos , Fosfofrutoquinase-2/genética , Transdução de SinaisRESUMO
Intravenous (i.v.) glucocorticoid is recommended for active moderate-to-severe thyroid-associated ophthalmopathy (TAO). However, the details of the treatment schedule are still debatable. The present prospective randomized trial was performed to compare clinical outcomes and serum cytokines between the two regimens. A cohort of 90 patients with active moderate-to-severe TAO was randomized to receive i.v. methyl prednisolone on a weekly protocol or daily scheme. The response rate was evaluated at the 12-week follow-up visit. Serum interleukin (IL)-2, IL-6 and IL-17 levels were measured in 160 patients with TAO, 60 patients with isolated Graves' disease (GD) and 60 normal control (NC) at baseline, as well as patients with active moderate-to-severe TAO at the 12th week after treatment. The daily scheme had a higher response rate than the weekly protocol without a significant difference (77.8 vs. 63.6%, P>0.05). No major adverse events were recorded under either regimen. Overall, minor events were more common on the daily scheme (11.36 vs. 4.35%, P<0.05)than on the weekly protocol, whereas the deterioration of eye symptoms (two patients) was only reported on the weekly protocol. At baseline, the IL-17 level in the TAO group was higher than that in the isolated GD and NC groups (P<0.05). In addition, the IL-17 level in the active TAO group was higher than that in the inactive TAO group (P<0.05). Furthermore, the IL-17 level had significantly decreased under the two regimens at the 12-week visit (P<0.05). In conclusion, for patients with active moderate-to-severe TAO, daily i.v. glucocorticoid therapy has a relative higher response rate than the weekly protocol with a few more minor adverse events. These two regimens have their own merits with regard to adverse effects. IL-17 has the potential to be a biomarker for evaluating TAO activity and treatment effects.
RESUMO
OBJECTIVE: To study the effect of polydatin on the expression level of miR-214 and liver function in atherosclerotic mice. METHODS: Forty male ApoE(-/-) mice were randomly allocated into 4 groups (n=10), namely the model group, low- and high-dose polydatin groups, and simvastin group, with 10 male C57BL/6J mice serving as the normal control group. Mouse models of atherosclerosis were established by feeding the ApoE(-/-) mice with a high-fat diet. After 12 weeks of treatment, blood levels of glucose, lipids, AST, and ALT and the contents of T-SOD and MDA in the liver tissue were detected. The pathologies of the liver were examined with HE staining, and miR-214 expression in the liver was detected using quantitative real-time PCR. RESULTS: Compared with the normal control mice, the mice in the model group showed significantly increased blood glucose, serum TC, TG, LDL-C, ALT, and AST levels, and MDA contents in the liver (P<0.01), with significantly decreased serum HDL-C level and SOD and miR-214 levels in liver (P<0.01). Polydatin treatment significantly ameliorated such changes in blood glucose, serum ALT, AST, TC, TG, LDL-C, and HDL-C levels, and MDA, SOD, and miR-214 contents in liver tissue (P<0.05). CONCLUSION: s Polydatin can reduce blood glucose and lipid levels and protect the liver function in atherosclerotic mice possibly by up-regulating the expression of miR-214 and T-SOD and down-regulating MDA in the liver.
Assuntos
Aterosclerose/tratamento farmacológico , Glucosídeos/farmacologia , MicroRNAs/metabolismo , Estilbenos/farmacologia , Animais , Apolipoproteínas E/genética , Glicemia/análise , Dieta Hiperlipídica , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/farmacologia , Lipídeos/sangue , Fígado/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Superóxido Dismutase/metabolismoRESUMO
BACKGROUND: The present study aimed to identify the relationship between glycemic variability (GV) and the 10-y risk of cardiovascular disease (CVD) in type 2 diabetes mellitus (T2DM) patients with good glycemic control. METHODS: Two-hundred forty consecutive T2DM patients (HbA1c≤7.0%) without CVD were included to calculate the 10-y CVD risk by Framingham risk score (FRS), and divided into 3 groups: low-risk group (FRS≤10%), intermediate-risk group (>10%, ≤20%) and high-risk group (>20%). Inter-group differences of GV were determined by comparing the SD of blood glucose (SDBG), mean amplitudes of glycemic excursion (MAGE), and mean of daily differences (MODD) gathered from 72-h continuous glucose monitoring system. RESULTS: The levels of SDBG and MAGE significantly increased along with the raises of 10-y CVD risk of T2DM patients (p<0.01). FRS was positively correlated with age, systolic blood pressure, SDBG and MAGE (r=0.717, 0.525, 0.509 and 0.485 respectively, p<0.01), while negatively correlated with the level of HDL-C (r=-0.348, p<0.01). Furthermore, multivariate logistic regression analysis confirmed that increased MAGE [OR: 1.623(1.198-2.316), p<0.001] and patients with high urine albumin excretion rates [OR: 1.743(1.247-2.793), p<0.001] were independent predictors for high 10-y CVD risk. CONCLUSION: GV predicts independently the 10-y CVD risk of T2DM patients with well-controlled HbA1c.
Assuntos
Automonitorização da Glicemia , Glicemia/análise , Doenças Cardiovasculares/sangue , Diabetes Mellitus Tipo 2/sangue , Hemoglobinas Glicadas/análise , Carga Glicêmica , Adulto , Feminino , Índice Glicêmico , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
Hepatitis B viral infection can lead to hepatitis B virus-associated glomerulonephritis, a clinically significant subtype of secondary nephritis. In the present study, we examined the presence of PreS1/S2 antigen in renal tissues by use of immunohistochemistry and investigated the use of PreS1/S2 and 2 HBV serum antigens, HBe-Ag and HBs-Ag, in the diagnosis. We assessed the presence of these 3 antigens in patients with confirmed hepatitis B virus-associated glomerulonephritis (n = 22) and patients without this disease (n = 19). Our results indicate that the combined use of PreS1/S2-Ag and serum HBe-Ag in the diagnosis of hepatitis B virus-associated glomerulonephritis had good positive predictive value (0.89), modest negative predictive value (0.77), and substantial agreement based on Cohen's kappa coefficient (κ = 0.660, P < 0.001). We suggest that our results be considered in the development of more definitive diagnostic criteria for hepatitis B virus-associated glomerulonephritis.