Endoplasmic reticulum stress suppresses lipin-1 expression in 3T3-L1 adipocytes.

Lipin-1 plays crucial roles in the regulation of lipid metabolism and cell differentiation in adipocytes. In obesity, adipose lipin-1 mRNA expression is decreased and positively correlated with systemic insulin sensitivity. Amelioration of the lipin-1 depletion might be improved dysmetabolism. Although some cytokines such as TNF-α and interleukin-1ß reduces adipose lipin-1 expression, the mechanism of decreased adipose lipin-1 expression in obesity remains unclear. Recently, endoplasmic reticulum (ER) stress is implicated in the pathogenesis of obesity. Here we investigated the role of ER stress on the lipin-1 expression in 3T3-L1 adipocytes. We demonstrated that lipin-1 expression was suppressed by the treatment with ER stress inducers (tunicamycin and thapsigargin) at transcriptional level. We also showed that constitutive lipin-1 expression could be maintained by peroxisome proliferator-activated receptor-γ in 3T3-L1 adipocytes. Activation of peroxisome proliferator-activated receptor-γ recovered the ER stress-induced lipin-1 suppression. These results suggested that ER stress might be involved in the pathogenesis of obesity through lipin-1 depletion.

Suppression of lipin-1 expression increases monocyte chemoattractant protein-1 expression in 3T3-L1 adipocytes.

Lipin-1 plays a crucial role in the regulation of lipid metabolism and cell differentiation in adipocytes. Expression of adipose lipin-1 is reduced in obesity, and metabolic syndrome. However, the significance of this reduction remains unclear. This study investigated if and how reduced lipin-1 expression affected metabolism. We assessed mRNA expression levels of various genes related to adipocyte metabolism in lipin-1-depleted 3T3-L1 adipocytes by introducing its specific small interfering RNA. In lipin-1-depleted adipocytes, mRNA and protein expression levels of monocyte chemoattractant protein-1 (MCP-1) were significantly increased, although the other genes tested were not altered. The conditioned media from the cells promoted monocyte chemotaxis. The increase in MCP-1 expression was prevented by treatment with quinazoline or salicylate, inhibitors of nuclear factor-κB activation. Because MCP-1 is related to adipose inflammation and systemic insulin resistance, these results suggest that a reduction in adipose lipin-1 in obesity may exacerbate adipose inflammation and metabolism.

Plasma soluble fibrin monomer complex as a marker of coronary thrombotic events in patients with acute myocardial infarction.

Soluble fibrin monomer appears in the bloodstream during the extremely early stage of blood coagulation and generally forms a complex with fibrinogen, termed soluble fibrin monomer complex (FMC). Determination of FMC can provide information regarding the state of thrombotic diseases; thus it is important to investigate whether FMC serves as an early indicator of myocardial infarction (MI). We investigated hemostatic and fibrinolytic parameters including FMC to determine their capabilities for indicating thrombotic conditions in the coronary artery. Blood samples from 47 patients with acute MI were obtained within 48 hours (acute phase) and during 120 - 600 hours (recovery phase), respectively, after MI onset. Plasma FMC was significantly elevated in the acute phase, compared with that during the recovery phase and in healthy controls (p = 0.001), suggesting that its elevation indicates thrombotic events in the coronary artery of MI patients. D-dimer, a marker of thrombus formation accompanied with fibrinolysis, was increased in both phases in the patients. In addition, FMC and D-dimer were significantly increased within 24 hours after onset as compared to 24 - 48 hours (p = 0.003 and p = 0.011). Furthermore, cardiac troponin T, a marker of myocardial damage, was significantly higher after 24 hours than within the first 24 hours (p = 0.001). Receiver operating characteristic (ROC) analysis of FMC for early MI diagnosis indicates that FMC, rather than D-dimer, is a better marker within 24 hours of onset. Measuring plasma FMC may be useful for early diagnosis of MI recurrence and deciding primary treatment.