ABSTRACT
OBJECTIVE Interleukin (IL)-1β, one of the principal inflammatory cytokines mainly secreted by mono?cytes and macrophages, is produced by cleavage of the inactive pro-IL-1βprecursor by caspase-1 via the NLRP3 inflam?masome complex. The fruits of Garcinia cambogia (Clusiaceae) are widely developed as health products for anti-obese purpose. 14-deoxygarcinol (DOG) is a polyisoprenylated benzophenone from the fruits of G. cambogia, which showed potent anti-inflammatory effect in our previous study. The objective of this study was to explore the anti-inflammatory mechanism of DOG and its roles in alleviating adipose tissue inflammation and insulin resistance. METHODS The anti-inflammatory effect of DOG was evaluated on LPS plus nigericin-induced THP-1 macrophages. The expression of NLRP3 inflammasome complex proteins was analyzed by Western blotting, immunofluorescence staining and co-immu?noprecipitation. The pro-inflammatory cytokines levels were determined by ELISA kits. RESULTS DOG increased the expression of Sirtuin 2 (SIRT2) deacetylase and enhanced its deacetylating activity to suppress the NLRP3 inflamma?some activation and IL-1βsecretion in THP-1 macrophages. Moreover, DOG attenuated macrophage conditioned medium-induced inflammatory responses in adipocytes and blocked THP-1 macrophages migration towards 3T3-L1 adipocytes. CONCLUSION DOG attenuated the inflammatory crosstalk between macrophages and adipocytes through SIRT2-mediated NLRP3 inflammasome inhibition, which might be used for the treatment of adipose tissue inflammation-related metabolic disorders.
ABSTRACT
To investigate the effects of leptin on glucose metabolism and related inflammatory factors in diabetic rats. Methods: Ten healthy male Wistar rats were randomly selected as the control group. Fifty rats were fed with high sugar and high fat diet and injected with streptozotocin (STZ, 25 mg/kg) intraperitoneally. They were randomly divided into model group, leptin low, middle and high dose group. The rats in the low, middle and high dose group were fed with leptin at the doses of 20, 50 and 100 μg/kg for 5 d respectively. Blood glucose (FBG) was measured by GOD-PAP method, insulin content (INS) was tested by radioimmunoassay, the serum levels of triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL-C) and high density lipoprotein (HDL-C) were determined by automatic biochemical analyzer, the contents of malondialdehyde (MDA), interleukin-6 (IL-6) and tumor necrosis factor (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA). Western blot was used to detect the expression of leptin in adipose tissue of diabetic rats. Compared with the control group, the blood glucose levels of other groups were increased significantly (P＜0.01). Compared with the model group, the blood glucose levels of middle and high dose leptin rats decreased significantly (P＜0.05, P＜0.01). The insulin level of high dose leptin group decreased significantly (P＜0.01). There was no significant difference in FBG and INS among the three groups (P＞0.05). Compared with the model group, TC levels of middle and high dose leptin group were decreased significantly (P＜0.05, P＜0.01). TG and LDL-C levels of high dose leptin group were decreased significantly (P＜0.05), HDL-C level of high dose group was increased significantly (P＜0.01). Compared with different dose groups, the high dose of leptin (100 μg/kg) could decrease the levels of TC, TG and LDL-C, and increase the level of HDL-C, which was better than those of the middle and low dose of leptin (P＜0.05) Compared with the model group (52.27±10.93), the levels of leptin in low, middle and high dose group were (47.35±12.09), (44.68±10.23) and (40.13±9.87) respectively, which could be decreased by leptin in a dose-dependent manner. The abnormal secretion of leptin is one of the factors inducing diabetes mellitus. Under the intervention of a certain concentration of exogenous leptin (100 μg/kg), it can significantly reduce the level of MDA, TNF-α, and improve the level of IL-6. The mechanism may be closely related to the reduction of inflammatory response, oxidative stress and correction of dyslipidemia. Leptin also reduces the risk of disease progression in diabetes treatment.
ABSTRACT
A fragment sized 400bp of White spot syndrome virus（WS SV，formerly de signated NOSV），recovered from recombinant plasmid pAFD, was labeled with Digox igenin as a probe to detect dynamic distribution of WSSV within 120h and 72h in crawfishes（Cambarus proclarkii） inoculated WSSV by oral taking and injecti on r espectively. Stomach epithelium, intestine epithelium, heart, gill, haemolymph, muscle, hepatopancreas, hypoderm, connective tissue and ovary of infected crawfi shes were examined for WSSV. In both groups, WSSV was first detected in heamoly mph at 12h p.i. and then disappeared. Again it was detected at 96h p.i. only in oral infection group and maintained till 120h p.i., but it didn't appear at 72h p.i. in injection group. WSSV in heart, muscle was detected at 36h p.i. in oral infection group and 24h p.i. in injection group respectively, and then increased generally. In addition, WSSV in intestine epithelium, connective tissue, ovary of oral infection group and intestine epithelium, hypoderm, ovary of injection g roup could also be detected. In dead crawfishes after 120h and 72h p.i. in two groups, WSSV could be detected in all the examined tissues and it demonstrated t hat systemic infection occurred in the animales. The tissue containing more amo unts of WSSV was hypoderm in oral infection group, while intestine epithelium, g ill, hypoderm, ovary in injection infection group. It deduced that WSSV first a ppears in haemolymph and then goes into heart, muscle and other tissues and prol iferates in them. Once again, WSSV is released into heamolymph resulting in syst emic infection till crawfishes' death.