Obesity is an increasingly severe socioeconomic health issue worldwide. Rodents with diet-induced obesity (DIO) are widely used as models of obesity. The main aim of this study was to establish a DIO model using Wistar lean (+/+ or +/−) rats by feeding a high-fat diet (45 kcal% fat) to dams during the latter term of gestation and the lactation period. A second aim was to examine the effect of post-weaning nutrition independently of maternal nutrition. Some pups (group D) were fed the same high-fat diet after weaning, while others (group C) were fed a chow diet after weaning. In the control groups, the dams were fed only the chow diet and the pups were fed either the chow diet (group A) or high-fat diet (group B) after weaning. Between 16–21 weeks of age, group D showed the heaviest body weight and visceral adipose tissue weight among groups, in addition to glucose intolerance and high concentrations of glucose and cholesterol in plasma. Group B showed mild obesity with dysfunctions in glucose and lipid metabolism. Interestingly, group C showed mild obesity and impaired glucose tolerance, similar to the phenotype of group B. In summary, the high-fat diet challenge of dams during gestation and lactation caused an increase in adipose tissue weight and abnormalities of glucose and lipid metabolism in their adult offspring. Our results suggest the importance of both maternal and post-weaning nutrition for DIO production and provide useful DIO models.

Objectives Convallatoxin (CNT) is a natural cardiac glycoside extracted from lily of the valley (Convallaria majalis). Although it is empirically known to cause blood coagulation disorders, the underlying mechanism remains unclear. CNT exerts cytotoxicity and increases tissue factor (TF) expression in endothelial cells. However, the direct action of CNT on blood coagulation remains unclear. Therefore, herein, we investigated the effects of CNT on whole blood coagulation system and TF expression in monocytes.Methods Blood samples were collected from healthy volunteers to measure plasma thrombin-antithrombin complex (TAT) concentration using ELISA and to perform rotational thromboelastometry (ROTEM) and whole-blood extracellular vesicle (EV)-associated TF (EV-TF) analysis. The effects of CNT were also investigated using the monocytic human cell line THP-1. Quantitative real-time PCR and western blotting were performed, and PD98059, a mitogen-activated protein kinase (MAPK) inhibitor, was used to elucidate the action mechanism of CNT-mediated TF production.Results CNT treatment increased EV-TF activity, shortened the whole blood clotting time in rotational thromboelastometry analysis, and increased TAT levels, which is an index of thrombin generation. Furthermore, CNT increased TF mRNA expression in THP-1 cells and EV-TF activity in the cell culture supernatant. Therefore, CNT may induce a hypercoagulable state with thrombin generation, in which elevated EV-TF activity derived from monocytes might be involved. These procoagulant effects of CNT were reversed by PD98059, suggesting that CNT-induced TF production in monocytes might be mediated by the MAPK pathway.

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