The Role Of Obesity In The Development Of Multiple Sclerosis

Background and purposeMultiple sclerosis(MS)is one of the common central nervous system(CNS)demyelinating diseases,and its pathogenesis and mechanism are still unclear.Epidemiological studies have shown that genetic factor and environmental factors are also important factors in the development of MS,including EBV infection,smoking,vitamin D levels,latitude,diet and gut microbiome and so on.Obesity is a risk factor of MS,and dyslipidemia may increase the progression of the disease by activating the inflammatory process in the vascular endothelium.In this study,we would like to explore whether obesity,as expressed by body mass index(BMI),is associated with the development and the severity of MS,and to evaluate the serum lipid profile(total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterin(LDL-C),high density lipoprotein cholesterin(HDL-C))and high sensitivity C reactive protein(hs CRP)in MS.Besides,we also evaluate the the role of obesity in the experimental autoimmune encephalomyelitis(EAE)animal model fed with high-fat diet(HFD).MethodsIn this retrospective study,238 patients with MS and 1190 healthy control(HC)were recruited.We called the patients,asked the information about the age when they first diagnosed with MS,their height and weight at that time and 19 years old and Expanded Disability Status Scale(EDSS)score.The body mass index(BMI)was calculated,and after stratifying the BMI group,the risk of MS was compared among subjects with different BMI by calculating the odds ratio(OR)with 95%confidence interval(CI).Besides,we collected the data of serum TC,TG,LDL-C,HDL-C,and hs CRP levels and assessed the relationship among lipid profile and hs CRP and BMI in enrolled patients.The animals were fed with different diets,including normal diet(ND)and HFD,and recorded the body weight every week,followed by immune induction.Then,we observed the clinical changes in mice,calculated the clinical scores,and spinal cord tissue taken from mice at the peak of disease to detect the degree of morbidity.ResultsThere was no statistical difference between different BMI groups and the development of MS compared to the normal weight population in adulthood,but subjects with BMI between 25 kg/m~2 to 30 kg/m~2 at adolescent(19 years old)had at least a 1.6-fold increased risk of developing MS compared with normal weight subjects,and those with BMI greater than or equal to 30 kg/m~2 had a higher risk,about 2.7-fold,and this effect was more significant in females.EDSS scores were correlated with BMI,especially at age 19(P<0.05,r=0.52)in MS patients,and EDSS scores also differed significantly among different BMI groups(P<0.0001).We also compared lipids and hs CRP levels in MS patients and HC in this case-control study and found that hs CRP was correlated with BMI in both MS patients and HC groups(HC group:P<0.0001;MS group:P=0.0004),and hs CRP levels were higher in MS patients than in HC group(P<0.05).Besides,TC(P<0.05)and LDL-C(P<0.0001)levels were higher and HDL-C levels were lower(P<0.01)in MS patients.We also confirmed the finding in an EAE model that HFD-induced obese mice have showed more severe neurologic dysfunction,increased morbidity,and earlier time to peak of the disease.ConclusionsHigher BMI(≥25 kg/m~2)at adolescent may increase risk of the development of MS,especially in female patients.The degree of neurologic disability of MS patients was correlated with BMI,and the neurological status of patients with higher BMI should be given more attention in clinical practice.The inflammatory response in MS patients is more obvious than in the HC group,and the higher degree of TC and LDL-C,and lower degree of HDL-C may have a negative impact on the development of MS.HFD-induced obese mice developed an exacerbated EAE.