No abstract

Pyroptosis is a novel type of programmed cell death associated with the pathogenesis of many inflammatory diseases. Docosahexaenoic acid (DHA) and Arachidonic acid (AA) is widely involved in inflammatory pathological processes. However, the effect and mechanism of DHA and AA on pyroptosis in Kupffer cells are poorly understood. The present study demonstrated that DHA and AA ameliorated lipopolysaccharide (LPS)-induced Kupffer cells pyroptosis by reversing the increased expression of NLRP3 inflammasome complex, GSDMD, IL-1β, IL-18, and PI-stained positive rate. Next, the study revealed that GPR120 silencing eliminated the anti-pyroptosis of DHA and AA in LPS-induced Kupffer cells, suggesting that DHA and AA exerted their effect through GPR120 signaling. Importantly, GPR120 endocytose and binds to NLRP3 under LPS stimulation. Furthermore, co-immunoprecipitation showed that DHA and AA promoted the interaction between GPR120 and NLRP3 in LPS-exposed Kupffer cells, thus inhibiting the self-assembly of NLRP3 inflammasome complex. Finally, the study verified that DHA and AA alleviated hepatic injury through inhibiting Kupffer cells pyroptosis in vivo. The findings indicated that DHA and AA alleviated LPS-induced Kupffer cells pyroptosis via GPR120 interaction with NLRP3, it might become a potential therapeutic approach hepatic injury.

The dose-dependent cytotoxicity induced by AgNPs may result from an interaction of oxidative stress, DNA damage and mitochondrial injury in A549 and HepG2 cells. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1691-1699, 2016.

diabetes, hypertension, etc. The causes of insulin resistance are complicated and may vary for different individuals. Nevertheless, the factor most commonly associated with insulin resistance is excess adiposity due to the increase in circulating fatty acids and ectopic lipids (1). Intramuscular lipids are an indispensable energy source for skeletal muscle. These lipids play pivotal roles in metabolism not only for skeletal muscle but also for the entire body. The accumulation of ectopic lipids in skeletal muscle is thought to be involved in the etiology of type II diabetes and insulin resistance by suppressing insulin-stimulated glucose uptake (2, 3). Skeletal muscle accounts for 80% of insulin-stimulated glucose uptake (4). It is the primary site of insulin-stimulated glucose uptake and metabolism (4, 5). Earlier studies, both in humans (6) and in animal models (7), indicated that intramuscular lipid accumulation was associated with insulin resistance, thereby providing a potential link between dysregulated fatty acid metabolism in skeletal muscle and insulin resistance (6-9). Zinc-2-glycoprotein (ZAG) is a 43 kDa soluble glycoprotein, first isolated from human plasma. However, a previous study showed that ZAG was produced in many tissues, Abstract Over the past two decades, intramuscular lipids have been viewed as a cause of insulin resistance due to their ability to suppress insulin-stimulated glucose uptake in skeletal muscle. Zinc-2-glycoprotein (ZAG) is an adipokine involved in lipolysis of white adipose tissue (WAT). To investigate the action of ZAG on insulin resistance induced by a high-fat diet (HFD), which affects the intramuscular fat, mice were divided into three groups, normal diet, HFD, and ZAG treatment under HFD (HFZ). The results showed that the insulin sensitivity of ZAG-treated mice was significantly improved. The body weight, WAT weight, and intramuscular fat were significantly decreased in the HFZ group compared with the HFD group. The lipolytic enzymes, including phosphorylation of hormonesensitive lipase and adipose triglyceride lipase, were significantly upregulated in the skeletal muscle of mice that received the ZAG treatment compared with the HFD group. Insulin signaling proteins, such as phosphorylation of insulin receptor substrate 1 and cell membrane glucose transporter type 4, were also significantly increased in the skeletal muscle of the ZAG-treated group. Furthermore, a metabolic rate study showed that ZAG overexpression increases the respiratory exchange ratio and heat production. In vitro, ZAG treatment promotes glucose uptake and decreases intracellular lipids in C2C12 myotubes. Taken together, these data showed that overexpression of ZAG alleviates HFD-induced insulin resistance in mice, along with decreasing the lipid content of skeletal muscle.-Gao, S-X., J. Guo, G-Q. Fan, Y. Qiao, R-Q. Zhao, and X-J. Yang. ZAG alleviates HFD-induced insulin resistance accompanied with decreased lipid depot in skeletal muscle in mice.

Zinc alpha2 glycoprotein (ZAG) is a new type of adipokine involved in adipose tissue mobilization, however, little is known about its lipid metabolism effect in liver. Therefore, we investigated the effects of ZAG in the regulation of hepatic lipid accumulation. Mice were randomly divided into two groups; one was fed a normal diet and another was fed a high-fat diet for eight weeks to establish obesity model. After that, the normal diet group was divided into ND (injection of pcDNA3.1) and NDZ (injection of ZAG recombinant plasmid) and the high-fat diet group was divided into HF (injection of pcDNA3.1) and HFZ (injection of ZAG recombinant plasmid). The mice were weighed once per week and injected with plasmid once every three days for eight times. The results showed that body weight and hepatic TG content were decreased dramatically in HFZ group compared with HF group. The stearoyl-CoAdesaturase1 (SCD1) and Acyl-CoA Synthetase-1 (ACSS1) protein levels in HFZ group were significantly decreased. Furthermore, phosphorylated hormone sensitive lipase (P-HSL) was significantly higher in HFZ group. In HFZ group, hepatic fatty acid translocase (CD36) and fatty acids binding protein-1 (FABP1) protein levels were reduced. In addition, the expression of phosphorylated protein kinase A (PPKA) in HFZ group was higher than the HF group. Meanwhile, NDZ group showed significantly decreased body weight and increased P-HSL level though the hepatic TG content showed no significantly changes compared with the ND group. Therefore, we conclude that ZAG may be beneficial for preventing high-fat-diet-induced hepatic lipid metabolic disorders.

No abstract

No abstract

The cytotoxicity and genotoxicity of AgNPs seems to occur mainly via particles uptake and the subsequent liberation of ions inside the cells. And furthermore, the GADD45α promoter-driven luciferase reporter cells, especially the HepG2-luciferase cells, could provide a new and valuable tool for predicting nanomaterials genotoxicity in humans.