Serum thromboxane B2 (TxB2) is a specific marker of platelet inhibition by aspirin. Yet, TxB2 levels differ by up to 10-fold between some aspirin-treated patient cohorts. This study aimed to identify factors responsible for differences in serum TxB2 between cohorts in the ADRIE study (n = 657) and the BOSTON study (n = 678) of aspirin-treated cardiovascular patients originally tested with different ELISA assays. TxB2 levels were assessed in representative subgroups of the two cohorts (34 samples in BOSTON and 39 in ADRIE) by both ELISAs, as well as liquid chromatography and tandem mass spectroscopy (MS). A multivariate analysis was performed on the whole cohort database to identify determinants of the difference of TxB2 levels between cohorts. There was no systematic bias between the original ELISA TxB2 values and the MS values and the median difference was small, 0.12 ng/ml, thus not explaining the difference between median TxB2 levels in the two study populations (7 and 0.6 ng/ml in the ADRIE and BOSTON studies, respectively). In the combined dataset of the ADRIE and BOSTON cohorts (n = 1342), body mass index, age, gender, aspirin dose, time from aspirin intake to blood draw, NSAID intake, platelet count and C-reactive protein were significantly associated with TxB2 levels. After adjustment for patient characteristics, the difference between cohorts did not decrease. Unexplained differences in serum TxB2 levels in different populations of aspirin-treated cardiovascular patients suggest that further studies are needed to confirm the role of serum TxB2 level as a prognostic factor or rather as a marker of therapeutic observance.

In small hibernators, global downregulation of the endocannabinoid system (ECS), which is involved in modulating neuronal signaling, feeding behavior, energy metabolism, and circannual rhythms, has been reported to possibly drive physiological adaptation to the hibernating state. In hibernating brown bears (Ursus arctos), we hypothesized that beyond an overall suppression of the ECS, seasonal shift in endocannabinoids compounds could be linked to bear’s peculiar features that include hibernation without arousal episodes and capacity to react to external disturbance. We explored circulating lipids in serum and the ECS in plasma and metabolically active tissues in free-ranging subadult Scandinavian brown bears when both active and hibernating. In winter bear serum, in addition to a 2-fold increase in total fatty acid concentration, we found significant changes in relative proportions of circulating fatty acids, such as a 2-fold increase in docosahexaenoic acid C22:6 n-3 and a decrease in arachidonic acid C20:4 n-6. In adipose and muscle tissues of hibernating bears, we found significant lower concentrations of 2-arachidonoylglycerol (2-AG), a major ligand of cannabinoid receptors 1 (CB1) and 2 (CB2). Lower mRNA level for genes encoding CB1 and CB2 were also found in winter muscle and adipose tissue, respectively. The observed reduction in ECS tone may promote fatty acid mobilization from body fat stores, and favor carbohydrate metabolism in skeletal muscle of hibernating bears. Additionally, high circulating level of the endocannabinoid-like compound N-oleoylethanolamide (OEA) in winter could favor lipolysis and fatty acid oxidation in peripheral tissues. We also speculated on a role of OEA in the conservation of an anorexigenic signal and in the maintenance of torpor during hibernation, while sustaining the capacity of bears to sense stimuli from the environment.

Grey mouse lemurs (Microcebus murinus) are primates that respond to environmental energetic constraints through strong physiological seasonality. They notably fatten during early winter (EW), and mobilize their lipid reserves while developing glucose intolerance during late winter (LW), when food availability is low. To decipher how the hepatic mechanisms may support such metabolic flexibility, we analyzed the liver proteome of adult captive male mouse lemurs, whose seasonal regulations are comparable to their wild counterparts. We highlight profound hepatic changes that reflect fat accretion in EW at the whole-body level, without triggering an ectopic storage of fat in the liver, however. Moreover, molecular regulations are consistent with the decrease in liver glucose utilization in LW, and therefore with reduced tolerance to glucose. However, no major regulation was seen in insulin signaling/resistance pathways. Fat mobilization in LW appeared possibly linked to the reactivation of the reproductive system while enhanced liver detoxification may reflect an anticipation to return to summer levels of food intake. Overall, these results show that the physiology of mouse lemurs during winter relies on solid molecular foundations in liver processes to adapt fuel partitioning while opposing the development of a pathological state despite large lipid fluxes.

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