Screening And Evaluation Of Spontaneous Ebesity Tree Shrew Model And Fat Transcriptome Differentially Expressed Gene

Obesity is a major public health problem that spans the world.The global prevalence of obesity continues to increase at an alarming rate.Obesity is an independent risk factor for cardiovascular disease,type 2 diabetes,cancer,osteoarthritis,and psychological disorders.It is imperative to clarify the pathogenesis and develop effective treatments.Obesity pathogenesis research,drug screening and evaluation are mostly carried out on rodents.Because of the species relationship,it is difficult for rodent obesity animal models to truly reflect the progress of human obesity.Therefore,looking for and creating an animal model similar to human obesity attracts much attention.Tree shrews are close relatives of primates or lower primates.In the artificially propagated tree shrew population,changes in health status,similar to human obesity,occur in tree shrews due to restrictions on movement during feeding and changes in diet structure/behavior patterns.This spontaneous obesity perfectly mimics the symptoms and causes of obesity in humans and is an excellent experimental material for the study of human obesity.Therefore,this study firstly investigated the spontaneous obese in tree shrew population and determined the grading standard of tree shrew obesity according to the obesity classification criteria of rats and humans.According to the criteria of preliminary classification,tree shrews were selected in 3 different obesity grades.Representative tree shrews,systematically observed and tested for metabolic parameters(body weight,body length,blood glucose,HbAlc,TC,TG,HDL,LDL),differences in fat composition,major organ pathology,and changes in intestinal flora of different tree shrews.Through the above investigation,we determined the criteria and grading of spontaneous obesity tree shrews.The tree shrew obesity was initially divided into normal(mean± 2 standard deviations)and moderate obesity(2 standard deviations<average<4 standard deviations).There were significant differences in body weight,blood glucose,HbA1c,TC,TG,HDL,LDL,and fat volume between tree shrews and severe obesity(mean>4 standard deviation).There are also involvement of different degree multi-organ damage and pathological changes in Moderate obesity and severe fat tree shrews.Intestinal flora diversity and the proportion of Bacteroidetes/Firmicutes is reduced.Various indicators,differences in fat composition,pathological changes,and changes in intestinal microbiota have proved that spontaneous obese tree shrews are an possible obesity animal model.Secondly,modern studies have found that adipose tissue in the body is not just a simple storage of fat,energy storage organ,plays an important role in the regulation of systemic fatty acid homeostasis,and can also secrete many hormones,cytokines and chemokines,etc.In order to study the molecular mechanism of fat in a spontaneous obesity,this work studied the transcriptome sequencing of tree fat of different degrees of obesity and analyzed the weighted gene coexpression network.Methods The correlation between the transcriptome differentially expressed gene modules of tree shrew adipose tissue and the quantification of obesity phenotypes,the analysis of tree shrew fat single nucleotide polymorphisms(SNPs)and variable shear(AS)were performed.The underlying gene IL-6,which influences obesity,has undergone in-depth basic research.The results showed that the three modules:translation,immune,and signaling pathways involved in the differential expression of the three genes were significantly associated with the obesity phenotype.GO annotations indicated that the "ribosome pathway" and "lysosome/proteasome pathway" genes are associated with obesity.High expression in tree shrews.KEGG analysis found that the keto acid metabolic pathway was highly expressed in moderately obese tree shrews,and the catabolism of phenylalanine and tyrosine was highly expressed in severe obese tree shrews.Through the correlation of genes in the regulatory network for the construction of differentially expressed genes,three core genes were identified,UBA52 in the translation related module,AKT1 in the immune related module,and LRRK2 in the signal pathway related module.The authors have reported a causal relationship between AKT1 and obesity in vitro and in vivo,but the specific mechanism has not yet been clarified.However,the association between UBA52 and LRRK2 and obesity has not been reported,and may play a key role in the development of obesity.We further screened 1187 SNP markers that may have been associated with adipogenesis and metabolism in the GO complications,77 GO annotations,and 1 080 fat transcriptomes annotated with the KEGG pathway;53 1 variable shear differences Sexual expression.Systematic analysis of the IL-6 gene revealed that the IL-6 gene of tree shrew is more closely related to humans and non-human primates than large mice,and it is very conservative for the key sites of receptor binding,and the tree shrew IL-6 The recording of receptors and signaling proteins further suggests that there may be a similar signaling cascade in tree shrews.In summary,this study systematically evaluated spontaneous obesity tree shrews and systematically described and evaluated models from phenotypic,physiological and biochemical indicators,changes in fat composition,pathological changes in major organs,and changes in intestinal flora.Spontaneous obese tree shrews have been shown to be in accord with or close to clinical animal models of obesity.At the same time,new potential molecular markers and obese target genes have been identified for the screening of fat differential genes and the construction of gene regulatory networks.These studies have established and explored the etiology and pathogenesis of obesity and new drugs for weight loss in tree shrew obesity models.The study of its target is of great significance.