The Acute-Phase Protein Orosomucoid Regulates Food Intake and Energy Homeostasis via Leptin Receptor Signaling Pathway.

The acute-phase protein orosomucoid (ORM) exhibits a variety of activities in vitro and in vivo, notably modulation of immunity and transportation of drugs. We found in this study that mice lacking ORM1 displayed aberrant energy homeostasis characterized by increased body weight and fat mass. Further investigation found that ORM, predominantly ORM1, is significantly elevated in sera, liver, and adipose tissues from the mice with high-fat diet (HFD)-induced obesity and db/db mice that develop obesity spontaneously due to mutation in the leptin receptor (LepR). Intravenous or intraperitoneal administration of exogenous ORM decreased food intake in C57BL/6, HFD, and leptin-deficient ob/ob mice, which was absent in db/db mice and was significantly reduced in mice with arcuate nucleus (ARC) LepR knockdown, whereas enforced expression of ORM1 in ARC significantly decreased food intake, body weight, and serum insulin level. Furthermore, we found that ORM is able to bind directly to LepR and activate the receptor-mediated JAK2-STAT3 signaling in hypothalamus tissue and GT1-7 cells, which was derived from hypothalamic tumor. These data indicated that ORM could function through LepR to regulate food intake and energy homeostasis in response to nutrition status. Modulating the expression of ORM is a novel strategy for the management of obesity and related metabolic disorders.

Hyperbaric oxygen preconditioning ameliorates blood-brain barrier damage induced by hypoxia through modulation of tight junction proteins in an in vitro model.

AIM: To explore the effects of hyperbaric oxygen preconditioning (HBOP) on the permeability of blood-brain barrier (BBB) and expression of tight junction proteins under hypoxic conditions in vitro. METHODS: A BBB in vitro model was constructed using the hCMEC/D3 cell line and used when its trans-endothelial electrical resistance (TEER) reached 80-120 Ω · cm2 (tested by Millicell-Electrical Resistance System). The cells were randomly divided into the control group cultured under normal conditions, the group cultured under hypoxic conditions (2%O2) for 24 h (hypoxia group), and the group first subjected to HBOP for 2 h and then to hypoxia (HBOP group). Occludin and ZO-1 expression were analyzed by immunofluorescence assay. RESULTS: Normal hCMEC/D3 was spindle-shaped and tightly integrated. TEER was significantly reduced in the hypoxia (P=0.001) and HBOP group (P=0.014) compared to control group, with a greater decrease in the hypoxia group. Occludin membranous expression was significantly decreased in the hypoxia group (P=0.001) compared to the control group, but there was no change in the HBOP group. ZO-1 membranous expression was significantly decreased (P=0.002) and cytoplasmic expression was significantly increased (P=0.001) in the hypoxia group compared to the control group, although overall expression levels did not change. In the HBOP group, there was no significant change in ZO-1 expression compared to the control group. CONCLUSION: Hyperbaric oxygen preconditioning protected the integrity of BBB in an in vitro model through modulation of occludin and ZO-1 expression under hypoxic conditions.

Curcumin prevents cerebral ischemia reperfusion injury via increase of mitochondrial biogenesis.

Curcumin is known to have neuroprotective properties in cerebral ischemia reperfusion (I/R) injury. However, the underlying molecular mechanisms remain largely unknown. Recently, emerging evidences suggested that increased mitochondrial biogenesis enabled preventing I/R injury. Here, we sought to determinate whether curcumin alleviates I/R damage through regulation of mitochondrial biogenesis. Sprague-Dawley rats were subjected to a 2-h period of right middle cerebral artery occlusion followed by 24 h of reperfusion. Prior to onset of occlusion, rats had been pretreated with either low (50 mg/kg, intraperitoneal injection) or high (100 mg/kg, intraperitoneal injection) dose of curcumin for 5 days. Consequently, we found that curcumin pretreatment enabled improving neurological deficit, diminishing infarct volume and increasing the number of NeuN-labeled neurons in the I/R rats. Accordingly, the index of mitochondrial biogenesis including nuclear respiratory factor-1, mitochondrial transcription factor A and mitochondrial number significantly down-regulated in I/R rats were reversed by curcumin pretreatment in a dose-dependent manner, and the mitochondrial uncoupling protein 2 presented the similar change. Taken together, our findings provided novel evidence that curcumin may exert neuroprotective effects by increasing mitochondrial biogenesis.