Combined Aerobic and Resistance Exercise Training Reduces Circulating Apolipoprotein J Levels and Improves Insulin Resistance in Postmenopausal Diabetic Women

BACKGROUND: Circulating apolipoprotein J (ApoJ) is closely associated with insulin resistance; however, the effect of exercise on circulating ApoJ levels and the association of ApoJ with metabolic indices remain unknown. Here, we investigated whether a combined exercise can alter the circulating ApoJ level, and whether these changes are associated with metabolic indices in patients with type 2 diabetes mellitus.METHODS: Postmenopausal women with type 2 diabetes mellitus were randomly assigned into either an exercise (EXE, n=30) or control (CON, n=15) group. Participants in the EXE group were enrolled in a 12-week program consisting of a combination of aerobic and resistance exercises. At baseline, 4, 8, and 12 weeks, body composition and metabolic parameters including homeostatic model assessment of insulin resistance (HOMA-IR) and serum ApoJ levels were assessed.RESULTS: In the EXE group, ApoJ levels decreased 26.3% and 19.4%, relative to baseline, at 8 and 12 weeks, respectively. Between-group differences were significant at 8 and 12 weeks (P<0.05 and P<0.001, respectively). In the EXE group, 12 weeks of exercise resulted in significant decreases in body weight, percent body fat, and HOMA-IR indices. Concurrently, weight-adjusted appendicular skeletal muscle mass (ASM/wt) was increased in the EXE group compared with the CON group. Importantly, changes in the ApoJ level were significantly correlated with changes in ASM/wt.CONCLUSION: Exercise training resulted in a significant decrease in the circulating ApoJ level, with changes in ApoJ associated with an improvement in some insulin resistance indices. These data suggest that circulating ApoJ may be a useful metabolic marker for assessing the effects of exercise on insulin resistance.

Effects of Rosuvastatin on Apolipoprotein J in Balloon-Injured Carotid Artery in Rats / Efeitos da Rosuvastatina sobre Apolipoproteína J em Artérias de Ratos Lesionadas com Balão

Abstract Background: Restenosis after percutaneous coronary intervention in coronary heart disease remains an unsolved problem. Clusterin (CLU) (or Apolipoprotein [Apo] J) levels have been reported to be elevated during the progression of postangioplasty restenosis and atherosclerosis. However, its role in neointimal hyperplasia is still controversial. Objective: To elucidate the role Apo J in neointimal hyperplasia in a rat carotid artery model in vivo with or without rosuvastatin administration. Methods: Male Wistar rats were randomly divided into three groups: the control group (n = 20), the model group (n = 20) and the statin intervention group (n = 32). The rats in the intervention group were given 10mg /kg dose of rosuvastatin. A 2F Fogarty catheter was introduced to induce vascular injury. Neointima formation was analyzed 1, 2, 3 and 4 weeks after balloon injury. The level of Apo J was measured by real-time PCR, immunohistochemistry and western blotting. Results: Intimal/medial area ratio (intimal/medial, I/M) was increased after balloon-injury and reached the maximum value at 4weeks in the model group; I/M was slightly increased at 2 weeks and stopped increasing after rosuvastatin administration. The mRNA and protein levels of Apo J in carotid arteries were significantly upregulated after rosuvastatin administration as compared with the model group, and reached maximum values at 2 weeks, which was earlier than in the model group (3 weeks). Conclusion: Apo J served as an acute phase reactant after balloon injury in rat carotid arteries. Rosuvastatin may reduce the neointima formation through up-regulation of Apo J. Our results suggest that Apo J exerts a protective role in the restenosis after balloon-injury in rats.

Resumo Fundamento: A reestenose após intervenção coronária percutânea (ICP) após doença coronariana continua um problema não solucionado. Estudos relataram que os níveis de clusterina (CLU), também chamada de apolipoproteína (Apo) J, encontram-se elevados na progressão da reestenose pós-angioplastia e na aterosclerose. Contudo, seu papel na hihperplasia neointimal ainda é controverso. Objetivo: Elucidar o papel da Apo J na hiperplasia neointimal na artéria carótida utilizando um modelo experimental com ratos in vivo, com e sem intervenção com rosuvastatina. Métodos: ratos Wistar machos foram divididos aleatoriamente em três grupos - grupo controle (n = 20), grupo modelo (n = 20), e grupo intervenção com estatina (n = 32). Os ratos no grupo intervenção receberam 10 mg/kg de rosuvastatina. Um cateter Fogarty 2 F foi introduzido para induzir lesão vascular. A formação de neoíntima foi analisada 1, 2, 3 e 4 semanas após lesão com balão. Concentrações de Apo J foram medidas por PCR em tempo real, imuno-histoquímica e western blotting. Resultados: A razão área íntima/média (I/M) aumentou após a lesão com balão e atingiu o valor máximo 4 semanas pós-lesão no grupo modelo; observou-se um pequeno aumento na I/M na semana 2, que cessou após a administração de rosuvastatina. Os níveis de mRNA e proteína da Apo J nas artérias carótidas aumentaram significativamente após administração de rosuvastatina em comparação ao grupo modelo, atingindo o máximo na semana 2, mais cedo em comparação ao grupo modelo (semana 3). Conclusão: A Apo J atuou como reagente de fase aguda após lesão com balão nas artérias carótidas de ratos. A rosuvastatina pode reduzir a formação de neoíntoma por aumento de Apo J. Nossos resultados sugerem que a Apo J exerce um papel protetor na reestenose após lesão com balão em ratos.

Therapeutic effect of transplantation of ApoJ-modified bone marrow mesenchymal stem cells on intracere-bral hemorrhage in rats and its action mechanism / 医学研究生学报

Objective The nerve-protective effect of Apoli-poprotein J ( ApoJ) in intracerebral hemorrhage ( ICH) is not yet clarified.This study aimed to explore the therapeutic effect of trans -plantation of bone marrow mesenchymal stem cells (BMSCs) carrying the ApoJ gene on intracerebral hemorrhage in rats and its possible ac -tion mechanism. Methods Rat BMSCs were isolated, cultured in vitro, and transfected with the recombinant plasmid pEGFP -N1-ApoJ mediated with lipofectamine.Ninety-six SD rats were randomly divided into groups A, B and C, and ICH models were established by two -step autologous intracranial blood injection .At 24 hours after model-ing, the rats in groups A, B, and C were transplanted with the same volume of ApoJ-transfected BMSC suspension, BMSC suspension and normal saline, respectively.At 1, 3, 5 and 7 days after transplantation, the neurofunction recovery of the rats were evaluated with modified Neurological Severity Scores (mNSS), the brain water content measured by the dry -wet weight method, and the expression level of complement component 3 (C3) in the brain tissue detected by Western blot . Results The mNSS exhibited no statistically significant differences among the three group of rats on the 1st day after transplantation (P>0.05), but was remarkably lower in group A than in B and C on the 3rd (8.13±0.99 vs 9.25±1.28 and 10.88±0.84, P<0.05), 5th (6.75±1.04 vs 8.50±1.41 and 9.75±0.89, P<0.05) and 7th day (5.63±0.52 vs 7.00±0.54 and 7.88±1.25, P<0.05), and markedly lower in group B than in C (P<0.05).The water content in the brain tissue was also significantly lower in group A than in B and C on the 1st (78.17±0.82 vs 78.83±0.56 and 80.38±0.35, P<0.05), 3rd (78.68±0.55 vs 79.12±0.26 and 81.47±0.26, P<0.05), 5th (77.00±0.58 vs 78.13±0.46 and 79.74± 0.41, P<0.05) and 7th day (75.89±0.46 vs 76.86±0.29 and 78.44±0.44, P<0.05), and remarkably lower in group B than in C (P<0.05).Western blot showed that the expression of the C 3 protein in the brain tissue was markedly decreased in group A as compared with B and C on the 1st (0.096±0.011 vs 0.212±0.014 and 0.440±0.006, P<0.05), 3rd (0.083±0.005 vs 0.164±0.013 and 0.604± 0.011, P<0.05), 5th (0.064±0.009 vs 0.105±0.010 and 0.333±0.010, P<0.05), 7th day (0.045±0.007 vs 0.091±0.004 and 0.141± 0.003, P<0.05), and significantly lower in group B than in C (P<0.05). Conclusion ApoJ can promote the recovery of the neuro-logical function of ICH rats by inhibiting complement activation -mediated secondary brain damage and alleviating cerebral edema .

Research advance of apolipoprotein J in brain injury / 中国法医学杂志

Apolipoprotein J plays an important role in neuroprotection and neurological restoration after brain injury. It shows spatiotemporal dynamic expression at varying times after brain injury. Thus, it will be of great importance in the clinical treatment of brain injury, as well as in post-injury intervals estimation in forensic pathology. In this paper, we will review relevant research advance of it in brain injury.

Expression Pattern of Apolipoprotein J in Rat's Model of Carotid Artery Restenosis / 中国循环杂志

Objective: To study the expression pattern of apolipoprotein J (Apo J) in rat's model of vascular restenosis after cartid balloon dilation. Methods: A total of 40 Wistar rats were randomly divided into 2 groups: Experimental group, the rat's model of carotid artery injury was established by 2 F Fogarty balloon catheter scratching in right carotid artery and Control group, the rats received sham operation without catheter scratching. n=20 in each group. Right carotid artery tissue was taken at 1, 2, 3, 4 weeks after the operation respectively and 5 rats were used for each time point. The morphological changes were measured by HE staining, protein and gene expressions of Apo J were examined by immunohistochemistry and qRT-PCR. Results: Compared with Control group, at each time point Experimental group had obvious intimal hyperplasia and up-regulated protein and gene expressions of Apo J, P<0.05. In Experimental group, with prolonged time of injury, consistent endometrial hyperplasia was observed and it reached the maximum at 4 weeks after operation; the peak protein and gene expressions of Apo J was found at 3 weeks after operation, then decreased at certain point at 4 weeks after operation, P<0.05. Conclusion: Apo J might be closely related to intimal hyperplasia after vascular injury, high expression of vascular Apo J was mainly derived from vascular smooth muscle cell synthesis, it could be a kind of compensation with protective role and might be used as a new biological target for treating vascular retenosis after percutaneous coronary intervention.