The adipocyte-derived secretory protein adiponectin functions as an insulin-sensitizing agent. In plasma, adiponectin exists as low, medium, and high molecular weight oligomers. Treatment with trans -10, cis -12 conjugated linoleic acid (t-10, c-12 CLA) reduces levels of adiponectin as well as triglyceride (TG) in mice and adipocyte cell culture models. The aim of this study was to determine whether the effects of t -10, c -12 CLA on adiponectin and TG are mediated through modulation of the transcription factor peroxisome proliferator-activated receptor g (PPARg). 3T3-L1 cells were treated either during or after differentiation into adipocytes with 100 mM t-10, c-12 CLA with or without 10 mM troglitazone, a PPARg agonist, or 1 mM GW9662, a PPARg antagonist, and adiponectin and TG levels were analyzed. Treatment with t-10, c-12 CLA reduced TG as well as cellular and secreted adiponectin levels and impaired the assembly of adiponectin oligomers. These changes were accompanied by decreases in PPARg mass. Troglitazone was able to reverse the t -10, c -12 CLA-mediated decrease in TG levels and restore the assembly of adiponectin oligomers but was unable to restore adiponectin synthesis. Conversely, treatment with GW9662 decreased TG mass and impaired adiponectin oligomer assembly but did not decrease total adiponectin mass. In a reporter assay, t-10, c-12 CLA appeared to be a partial PPARg agonist and prevented the stimulation of reporter activity by troglitazone. Therefore, the t-10, c-12 CLA isomer appears to alter adipocyte adiponectin metabolism through PPARg-dependent and PPARgindependent mechanisms.-Miller, J. R., P. Siripurkpong, J. Hawes, A. Majdalawieh, H-S. Ro, and R. S. McLeod. The trans-10, cis-12 isomer of conjugated linoleic acid decreases adiponectin assembly by PPARg-dependent and PPARgindependent mechanisms. J. Lipid Res. 2008. 49: 550-562.

During torpor in a hibernating mammal, decreased blood flow increases the risk of blood clots such as deep vein thrombi (DVT). In other animal models platelets, neutrophils, monocytes and von Willebrand factor (VWF) have been found in DVT. Previous research has shown that hibernating mammals decrease their levels of platelets and clotting factors VIII (FVIII) and IX (FIX), increasing both bleeding time and activated partial throm-boplastin time. In this study, FVIII, FIX and VWF activities and mRNA levels were measured in torpid and non-hibernating ground squirrels (Ictidomys tridecemlineatus). Here, we show that VWF high molecular weight multimers, collagen-binding activity, lung mRNA and promoter activity decrease during torpor. The VWF multimers reappear in plasma within 2 h of arousal in the spring. Similarly, FIX activity and liver mRNA both dropped threefold during torpor. In contrast, FVIII liver mRNA levels increased twofold while its activity dropped threefold, consistent with a post-transcriptional decrease in FVIII stability in the plasma due to decreased VWF levels. Finally, both neutrophils and monocytes are decreased eightfold during torpor which could slow the formation of DVT. In addition to providing insight in how blood clotting can be regulated to allow mammals to survive in extreme environments, hibernating ground squirrels provide an interesting model for studying.

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The objective of this study is to determine how a hibernating mammal avoids the formation of blood clots under periods of low blood flow. Hibernating ground squirrels have dramatically decreased heart rates (3‐5 beats per minute) and blood flow, which should put them at risk of forming deep vein thrombi. In response, they have several adaptations during hibernation that prevent blood clotting, including 3‐fold decreases in Factors VIII and IX, and 10‐fold decreases in platelets. During hibernation, platelets are maintained at temperatures of 4‐8°C for up to six months. Within two hours of arousal, platelet levels return to normal, are not rapidly cleared from circulation, and are still functional. We have shown that in addition to decreased clotting factors, ground squirrels have a 10‐fold decrease in von Willebrand factor (vWF) protein and a 3‐fold decrease in vWF mRNA during hibernation. Platelets adhere to exposed collagen in a wound through binding to vWF, and unlike other mammalian platelets, cold storage of ground squirrel platelets does not increase binding of vWF. Ground squirrel platelets are also atypical in that their microtubules are cold‐resistant and change in shape from a circumferential ring to an equatorial rod once they reach 20ºC. This shape change was originally thought to trap the platelets in the spleen, but splenectomized and sham operated ground squirrels had the same platelet levels during torpor and interbout arousal, suggesting storage in an extrasplenic location. Finally, no evidence of irreversible cardiac ischemic damage was observed during hibernation through either histological staining or blood markers including troponin T, lactate dehydrogenase and creatine kinase. Taken together, these results suggest that ground squirrels avoid deep vein thrombosis by reversibly decreasing platelet levels and activity during hibernation. Grant Funding Source: Supported by NIH grant 2R15HL093680‐02

Background: We developed and validated an algorithm to evaluate pure red cell aplasia (PRCA) incidence in chronic hepatitis C (CHC) patients in a large observational database. Methods: We conducted a retrospective study using the HealthCore Integrated Research Database