| Dietary fats provide the body with essential nutrients,and serve as one of energy sources and regulate the homeostasis of energy in the body.However,the effects of different dietary fats intake on health were not clearly enough.In this study,we characterized the alteration and distribution of fatty acids(FAs)in the liver,visceral fats(perienteric,epididymal and perirenal fat),spleen,brain,skeletal muscle and heart of SD rats fed with palm oil,lard,colleseed oil,sunflower oil and linseed oil.The mechanism of influences of different dietary fats on the fat homeostasis imbalance was investigated by using lipidomics,metabolomics and molecular biology methods.This research would provide a fundamental understanding to elucidate the effects of long-term intake of different dietary fats on metabolism,as well as on lipid homeostasis.The main studies and results are as follows.(1)The effect of dietary fat on the composition of FAs in rat organs was investigated.The results showed that the predominant FAs in the dietary fat significantly elevated the content of corresponding FAs and their derived FAs in rat organs,and high correlations between them were observed,especially in the liver and three visceral fats.palm oil(POG)intaking elevated significantly the levels of palmitic,palmitoleic,oleic and linoleic acid in tissues;lard(LOG)intaking elevated markedly the content of palmitic,stearic,oleic and linoleic acid in organs;oleic acid level in the organs of rats in the colleseed oil group(COG)significantly increased;sunflower oil(SOG)intaking elevated markedly the levels of oleic,gamma-linolenic,DGLA,ARA and linoleic acid in rats;levels of ?-linolenic acid,EPA and DHA in rats of the linseed oil group(LSOG)showed significant increases.Meanwhile,the FAs composition in major organs of lipid metabolism was more sensitive to alterations in exogenous FAs,whereas the FAs content of non-major lipid metabolism organs including the spleen,corresponding to predominant FAs in the dietary fat,also increased significantly but later than that in the major organs of lipid metabolism.In addition,as the liver-adipose tissue axis,the association of FAs in liver and visceral fats were more significantly connected with FAs in peripheral organs,suggesting that both played important roles in FAs regulation throughout the body.(2)The effects of excessive intake of different dietary fats on rat liver metabolism were further investigated.Based on untargeted metabolomics by UPLC-MS/MS,we found that the metabolic effects of different dietary fats on rat liver were different,however,the differential metabolites in each high-fat(HF)group participated in metabolic pathway of unsaturated fatty acid biosynthesis.Each high-fat group has unique metabolites in the liver,and all of these metabolites are associated with hepatic steatosis,oxidative stress,inflammation and even liver pathology,as well as reflecting adaptive regulation of the liver.The livers in POG,LOG,COG,SOG and LSOG had 9,3,4,3 and 4 specific metabolites respectively,including an eventual down-regulation in the abundance of glutathione(POG)and L-proline(SOG),which have antioxidant effects;LPC abundance reflecting hepatotoxicity and metabolic disorders eventually appeared to be upregulated,such as Lyso PC(0:0/18:0)in POG and Lyso PC(18:0/0:0)in SOG;upregulation of the final abundance of lipid metabolites reflecting increased oxidation level in livers,such as 8(R)-HPODE in LOG,Cholesta-4,6-dien-3-one,15H-11,12-EETA in COG and 9,10-Ep OME in LSOG;the abundance of lipid metabolites reflecting hepatic lipid accumulation and the development of NALFD eventually appeared to be upregulated,such as8(R)-HPETE in POG,S1 P in LOG,and 3-hydroxybutyric acid in LSOG.These data suggested that excess intake of different dietary fats affected liver normal metabolism as well as lipid homeostasis.(3)The effects of excessive dietary fat intake on the lipidome of visceral fats were examined.Using UPLC-MS/MS-based lipidomics and machine learning methods,it was found that changes in lipid composition in visceral fats were mainly occurred in the middle and early stages of the experiment,and that the levels of most of the differential lipids were found to be down-regulated,but all of the DGs containing fatty acyl chains corresponding to the predominant fatty acids in dietary fat were increased,e.g.,DGs containing C16 fatty acyl chains in the visceral fats of POG.Random forest regression and partial correlation analysis revealed associations between lipids containing similar fatty acyl chains,such as TG 54:6;1O and TG56:8 in epididymal fat in the POG,TG 52:2 and DG 32:0 in epididymal fat in the COG,and DG 36:6 and TG 54:9 in epididymal fat in LSOG.The differential lipids of perienteric and epididymal fat were mostly long-chain TG,whereas the differential lipids of perirenal fat contained fatty acids.This may be related to the location of these adipose tissues.(4)By characterizing the expression of 9 lipid metabolism-related genes including SCD,in liver and visceral fats,and their association with organ FAs and differential substances,our study further explored the mechanisms by which different dietary fats affect lipid homeostasis.The results revealed that some lipid metabolism genes appeared to be adaptively expressed when encountered with new dietary fat interventions,such as SCD,PPARs,etc.The expression of these genes mostly showed a tendency to be promoted at the beginning of the experiment.The expression of leptin and adiponectin were significantly promoted in all three visceral fats,while the expression of Adipo R2 was inhibited.The levels of derived FAs in organs such as palmitoleic acid showed a significant positive correlation with SCD expression in the group with high SFA content in dietary fat,the levels of the dominant FAs in tissues were positively correlated with the levels of adiponectin in the group with high UFA content in dietary fat,such as oleic acid in COG and ?-linolenic acid in LSOG.In addition,the expression of Adipo R2 in the liver was negatively correlated with the abundance of creatine and glutathione.The levels of DG in visceral fats,especially those containing the C18:3 fatty acyl chain,were significantly and positively correlated with the expression of LPL and adiponectin,whereas the levels of TG were significantly and negatively correlated with the expression of these two genes.These data indicated that different dietary fats affected the regulation of lipid homeostasis involved in the adipose tissue-liver axis by inhibiting Adipo R2 expression.Organisms would spontaneously adjust the expression of genes related to lipid metabolism to meet the demand for new dietary fats when their original lipid homeostasis was challenged.However,chronic overconsumption of dietary fat caused lipid accumulation and oxidation levels elevation in the liver,leading to inhibition of Adipo R2,which in turn caused adiponectin fail to function,resulting in inhibition of some lipid metabolism genes and disrupting lipid metabolism homeostasis.And this was independent of the saturation of dietary FAs but was related to the amount of dietary fat consumed.In addition,differences were found in the expression of genes related to lipid metabolism in different locations of visceral fats,for example,the expression of ACC1 in POG changed slightly in perienteric fat,while it was always significantly suppressed in epididymal fat,and showed a significant decrease over time in perirenal fat,suggesting that different locations of visceral fats had different functions in lipid metabolism,possibly related to their location. |
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