Acylation-stimulating protein (C3adesArg/ASP) is an adipokine that acts on its receptor C5L2 to stimulate triglyceride (TG) synthesis in adipose tissue. The present study investigated ASP levels in mouse models of obesity and leanness and the effect of ASP deficiency in C3 knockout (C3KO) mice on adipose tissue morphology. Plasma ASP levels in wild-type (WT) mice correlated positively with plasma nonesterified fatty acids (NEFA) (R ϭ 0.664, P Ͻ 0.001) and total cholesterol (R ϭ 0.515, P Ͻ 0.001). Plasma ASP was increased by 85% in obese ob/ob leptin-deficient mice and decreased in lean diacylglycerol acyltransferase 1 (DGAT1) KO mice (Ϫ54%) and C/EBP␣ ␤/␤ transgenic mice (Ϫ70%) compared with WT. Mice lacking alternative complement factor B or adipsin (FBKO or ADKO), required for ASP production, were also ASP deficient. Both FBKO and C3KO mice had delayed postprandial TG and NEFA clearance on low-fat (LF) and high-fat (HF) diets, suggesting that lack of ASP, not C3, drives the metabolic phenotype. Adipocyte size distribution in C3KO mice was polarized (increased number of both small and large cells), with decreased adipsin expression (Ϫ33% gonadal HF), DGAT1 expression (Ϫ31% to Ϫ50%) and DGAT activity (Ϫ41%). Overall, a reduction/deficiency in ASP is associated with an antiadipogenic state and ASP may provide a target for controlling fat storage. C3adesArg; complement C3; factor B; diacylglycerol acyltransferase 1; postprandial lipemia ACYLATION-STIMULATING PROTEIN (ASP/C3adesArg) is an adipose tissue-derived hormone that stimulates adipocyte triglyceride (TG) synthesis and glucose transport (20, 43). ASP acts through its receptor C5L2, a G protein-coupled receptor, to stimulate diacylglycerol acyltransferase (DGAT) activity, the rate-limiting enzyme in the TG synthesis pathway, and glucose transport (17,18).It has been suggested that ASP is generated through the alternative pathway of complement activation, based on differentiation-dependent expression of adipsin (factor D), complement C3, and factor B (FB) in adipose tissue (4, 5); however, this has not been shown directly. C3 convertase of the alternative pathway, a proteolytic complex formed by the interaction of C3b, FB, and adipsin (factor D), cleaves the third complement component (C3) into C3a and C3b (8). C3a is a potent anaphylatoxin interacting with its receptor C3aR. However, in the circulation, the terminal arginine of C3a is rapidly cleaved by carboxypeptidase B, inactivating the C3a anaphylatoxic function and generating C3adesArg (ASP) (8). Both ASP/C3adesArg and C3a interact with the receptor C5L2 to effectively stimulate TG synthesis in cultured adipocytes (18).C3 knockout (C3KO) mice are obligatorily ASP deficient, since they lack the precursor protein. We have previously reported that C3KO mice are lean yet hyperphagic (22, 40); the increased energy intake is being balanced by an increased energy expenditure (40). C3KO mice also displayed an altered plasma lipoprotein profile, mainly characterized by delayed postprandial TG clearance (23,24,40)...

It has been reported by us and other groups that the expression of small GTP binding protein RhoB can be induced by genotoxic stressors and glucocorticoid (GC), a stress hormone that plays a key role in stress response. Until now stress-induced genes that confer cytoprotection under stressed conditions are largely unknown. In this study, we investigated the effects and mechanism of non-genotoxic stressors, including scalding in vivo and heat stress in vitro on the expression of RhoB. We found for the first time that both scalding, which could induce typical neuroendocrine responses of acute stress and cellular heat stress significantly increased the expression of RhoB at mRNA and protein levels. Moreover, in vitro experiments in human lung epithelial cells (A549) showed that induction of RhoB by heat stress was in a glucocorticoid receptor (GR)-independent manner and through multiple pathways including stabilization of RhoB mRNA and activation of p38 MAPK. Further experiments demonstrated that up-regulation of RhoB significantly inhibited heat stress-induced apoptosis and elevated transcriptional activity of NF-κB, but did not affect the expression of Hsp70 in A549 cells. In conclusion, we showed for the first time that RhoB was up-regulated by scalding in vivo and heat stress in vitro and played an important cytoprotective role during heat stress-induced apoptotic cell death.

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Background. The neurotrophic pathway regulated by the brain-derived neurotrophic factor (BDNF) plays a crucial role in the pathogenesis of poststroke depression (PSD). How the traditional Chinese medicine compound preparation Xingnao Jieyu (XNJY) decoction regulates the neurotrophic pathway to treat PSD is unclear. Objective. This study aimed to investigate the antidepressant effect of XNJY decoction on a rat model of PSD and the molecular mechanism intervening in the neurotrophic pathway. Methods. After a middle cerebral artery occlusion model was established, chronic unpredictable mild stress was applied for 21 days to prepare a PSD model. XNJY groups and a fluoxetine (Flu) group of rats were intragastrically administered with XNJY and Flu, respectively, for 21 consecutive days. Depressive-like behaviors, including sucrose preference, open field test, and forced swimming test, were assessed. The survival and apoptosis of cortical and hippocampal neurons were evaluated by immunofluorescence assay and TUNEL staining. The contents of serotonin (5-HT), norepinephrine (NE), and BDNF in the cortex and hippocampus were determined by ELISA. The protein levels of BDNF, p-ERK/ERK, and p-CREB/CREB in the cortical and hippocampal regions were tested by Western blot. Results. The depressive-like behaviors markedly improved after XNJY and Flu treatment. XNJY and Flu promoted neuronal survival and protected cortical and hippocampal neurons from apoptosis. XNJY also increased the contents of 5-HT, NE, and BDNF and recovered the protein levels of p-ERK/ERK, p-CREB/CREB, and BDNF in the cortical and hippocampal regions. Conclusion. These results indicated that the XNJY decoction exerts an obvious antidepressant effect, which may be due to the regulation of the BDNF/ERK/CREB signaling pathway.

Inhalation of aerosolized PS generated by the noninvasive apparatus could significantly reduce lung injury, while using oxygen line available in the clinical wards to generate PS aerosol is more convenient and adds further benefits. This method can also be used to deliver Dex and other therapeutic agents to ameliorate lung injury.