Lipidomic Signature Of Lipid Deposition And Lipidolysis Metabolism In Porcine Adipose Tissues And Cross-species Comparison

Adipose tissue is a highly active endocrine organ and have important roles in energy metabolism.Adipose tissue is economically important in pig breeding,especially the lipid deposition and metabolism.Recently,the molecular mechanisms of the regulation of lipid metabolism have been extensively studied.However,the changes from gene regulation to phenotypes is unknown.Metabolomics is the link between genotypes and phenotypes.Lipidomics,a branch of metabolomics,can describe the characteristics of all lipids and provide relevant lipid metabolic functions.These phenotypic data can widely be used in fat deposition and lipolysis of pig.In this study,we obtained the adipocyte size and homogeneity of pig by gamma distribution function model and compared with other 11 species.Meanwhile,we used an untargeted metabolomic approach to detect a total of 456 samples（pig,mouse,rat and human）,systematically analyze lipidomic signature of pig adipose tissues in different locations during lipid deposition and lipolysis progress,tried to find the changes in lipid composition and lipid profile,and compared with other model animals and humans.The major results are listed as following:（1）.Simulating the distribution of adipocytes by gamma distribution function model to obtain the cell size and homogeneity.The adipocyte size and homogeneity of adipose tissue in different locations of pig were slightly different.Wild boar adipocyte size was significantly smaller than the Bama minipig,and the cell homogeneity was greater than it(P_mean<0.001 and P_SD<0.001).（2）.We compared pig adipocyte size and homogeneity to 11 species,including sheep,cat,dog,mouse,rat,rabbit,human,chicken,duck,goose,and Chinese sturgeon.Pig have significantly larger adipocyte size and lower cell homogeneity than other specie.Adipocyte phenotypic differences that were of evolutionary significance.The average adipocyte size in mammals were larger than that of avians,and the cell homogeneity were lower than that of avians(P_mean<0.01 and P_SD<0.01).The reptiles adipocyte size and homogeneity were similar to mammals(P_mean=0.53 and P_SD=0.35),and the reptiles and avians were significantly different(P_mean=0.09 and P_SD=0.07).（3）.We obtained a total of 456 samples lipidomic data of adipose tissue in different location of pig,mouse,rat and human.A total of 2,943 features（NIM）and 4,906features（PIM）were detected,of which 51.61%（2,532/4,906）and 44.55%（1,311/2,943）features were identified.（4）.The comparison of lipidomic profile between adipose tissues in different locations were detected.We observed tissue-specific differences between SAT and VAT.GOM exhibited a distinct lipidomic profile to ULB,and RAD was closer to ULB.This lipidomic profile in tissue-specific differences was consistent in pig and human.The higher abundant metabolites of SAT were mainly enriched in sphingomyelin metabolism,glycerophospholipid metabolism and linoleic acid metabolism.The higher abundant metabolites of VAT were widely involved in lipid lipogenesis and lipidolysis,fatty acid synthesis and metabolism and inflammation-related response.（5）.The lipidomic profile of adipose tissues in same location between mouse and rat was similar.The negative ion lipidomic profile of SAT and VAT（consistent position）between pig and human were similar.（6）.In the process of weight gain and weight loss,all adipose tissue increased adipocyte size（hypertrophy）after weight gain,and decreased adipocyte size（shrink）after weight loss（P_T<0.01）.Under normal diet,the difference of adipocyte size between tissues was not observed,but the difference was prominent after dietary changes(P_C=0.58,P_WG<0.01,P_WL<0.01).In the process of weight gain and weight loss,all adipose tissue cell homogeneity decreased after weight gain,and increased after weight loss（P_T<0.01）,which reflected the lipid turnover activity.Under normal diet,the difference of adipocyte homogeneity between tissues was not observed,but the difference was prominent after energy changes(P_C=0.16,P_WG<0.01,P_WL<0.01).（7）.The weight gain and weight loss in pig displayed the process of lipid lipogenesis and lipidolysis in pig adipose tissue.VAT of pig in response to weight gain were more sensitive than SAT,while SAT was blunt.（8）.Under energy excess,mouse i WAT and g WAT（hyperplasia and hypertrophy coexist）fat storage capacity increased by recruitment of new adipose cells from differentiation of self-renewing precursorcells,and by enlargement of mature adipose cells through lipogenesis,while pig and rat adipose tissues fat storage capacity only increased by enlargement of mature adipose cells through lipogenesis.The results suggested the regulation mechanism of lipid deposition may different among mouse,rat and pig.（9）.This study showed the diet-induced energy change promoted an overall remodelling of the lipidome in adipose tissues.However,adipose tissues metabolic status still accompanied negative influence by weight gain after weight loss.（10）.Pig adipose tissues exhibited a distinct lipidomic profile with rodent in responded to high-fat diet.Rat and mouse g WAT have similar lipidomic signature with the GOM and MAD of pig in responded to high-fat diet by altering their lipid composition.The functions of these lipids might conserved among the three species,which mainly involved in sphingomyelin metabolism and glycerophospholipids metabolism.All above,this study provided insight into lipidomic signature and of pig adipose tissues in different locations during lipid deposition and lipolysis progress.Meanwhile,we provides resource data for adipose tissue cell size,homogeneity and lipid metabolism characteristics in multi-species.