Abstract
Obesity is one of the main health problems in industrialized countries. The contribution of multiple factors developed in obesity can hardly be modeled in vitro. In this context, the development of animal models mimicking human obesity could be essential. The aim of the present study was to compare platelets from a diet-induced obesity (DIO) rat model with their lean control group in order to elucidate platelet dysfunction mechanisms in obesity and correlate the results with previous data from morbid obese patients. In parallel, we also established a blood collection and platelet isolation methodology to study the DIO rat model at biochemical and functional level. Optimal blood collection was obtained from vena cava and platelet isolation was based on a serial of centrifugations avoiding platelet activation. Our results show that the DIO rat model simulate obesity pathologically since weight gain, fasting glucose and platelet counts are increased in obese rats. Interestingly, platelet levels of the active form of Src (pTyr419) showed a tendency to increase in DIO rats pointing towards a potential dysfunction in Src family kinases-related signalling pathways in obesity. Moreover, platelets from DIO rats adhere more to collagen compared with the control group, pointing towards Glycoprotein VI (GPVI) as one of the dysregulated receptors in obesity, in agreement with our recent studies in humans. These results confirm that obesity, in line with human studies, present a platelet dysregulation, and highlight the relevance of considering novel antithrombotic drug targets in these patients, such as GPVI.
Highlights
Obesity is one of the main health problems in industrialized countries
We have recently performed some studies with platelets from morbid obese patients, comparing them with their lean-matched controls, where we found an alteration in Src family kinases (SFKs) signalling pathways, especially Glycoprotein VI (GPVI) in obesity[9,10]
The diet-induced obesity (DIO) rat model mimics the pathological characteristics of obesity. 40 adults Sprague–Dawley rats were provided free access to standard diet (10% fat) for a 1‐week baseline period
Summary
Obesity is one of the main health problems in industrialized countries. The contribution of multiple factors developed in obesity can hardly be modeled in vitro. The aim of the present study was to compare platelets from a diet-induced obesity (DIO) rat model with their lean control group in order to elucidate platelet dysfunction mechanisms in obesity and correlate the results with previous data from morbid obese patients. In line with the above, the second goal of the present study was to characterize the impact of obesity in DIO rat platelets and try to correlate their biochemical parameters with those we previously obtained in humans In this way, both the animal model and our previous clinical data would be cross validated helping at the same time to elucidate platelet dysfunction in obesity
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