The Role And The Mechanism Of Platelets In Obesity

Background and objectiveObesity,especially central obesity is associated with many diseases and it has been a key issue of public health.Obesity is a condition where adipose tissue enlarged by excess body fat accumulates.Usually,adipose tissue may enlarge by hyperplasia(increasing the number of adipocytes)and hypertrophy(increasing the size of adipocytes).Previous studies found that the quantity and activation of platelets were higher in obese individuals.The surface receptors of platelets are the contacts between platelets and their external world.Activated platelets can also release a number of proteins and small molecules that could promote cell proliferation.However,the mechanism of platelets on pre-adipocyte proliferation is still unclear.Therefore,to identify the role and the mechanism of platelet on obesity,we first investigated the associations between platelet indices and body fat mass and fat distribution in the population study.Second,the present study aims to clarify the mechanism of platelets on the proliferation of pre-adipocytes.MethodsPopulation study:A total of 3,327 individuals aged 18-80 years old were enrolled.Fat mass and fat distribution was assessed by the dual-energy X-ray absorptiometry.Blood samples were collected to measure metabolic profiles and platelet indices,including platelet quantity index(platelet count(PLT)),and platelet activation indices(mean platelet volume(MPV),plateletcrit(PCT),platelet distribution width(PDW),and platelet large cell ratio(PLCR)).Adjusted multivariate linear regression model was used to identify the associations of platelet indices with fat mass and fat distribution.ResultsPopulation study:Both PLT and PCT were positively associated with body mass index,waist circumference,waist hip ratio,total fat mass,total fat mass percentage,trunk fat mass percentage,android fat mass percentage,and android to gynoid fat ratio,and was negatively associated with gynoid fat mass percentage.The associations remained significantly even after adjusting high sensitivity C-reactive protein or white blood cell count.No significant associations were found between other three platelet indices(MPV,PDW,and PLCR)with fat mass or fat distribution.Experimental study:Our data demonstrated that both platelets and the release of activated platelets increased the pre-adipocyte proliferation.Furthermore,platelets and the release of activated platelets increased the 3T3-L1 cell proliferation and G0/G1-S cell cycle progression.Finally,we found that platelets promoted the proliferation of 3T3-L1 cells via Akt/mTOR pathway.Besides,we found that the proliferation of 3T3-Llcells treated with platelets from obese mouse elevated higher than platelets from normal mouse.ConclusionsOur population study found that only PLT and PCT were associated with fat mass and fat distribution.As PCT is mainly explained by PLT,these associations suggested that platelet quantity was more closely related to fat mass and fat distribution.These experimental results indicated a novel mechanism of platelets which promoted the proliferation of 3T3-L1 cell via Akt/mTOR pathway.