Effects Of High-fat Diets On Hepatic Endoplasmic Reticulum Stress And Inflammation And Their Reponses To Low-fat Diet Intervention

Part1Differential effects of high-fat diets enriched with lard oil or soybean oil on the incidence of obesity and related metabolic disordersObjective To investigate the effects of high-fat diets enriched with lard oil or soybean oil on the incidence of obesity and related metabolic disorders and estimated their responses to low-fat diet intervention.Methods Male SD rats were randomly assigned to LF group fed with standard food (n=10) and two isoenergetic high fat diet group fed with diet enriched with lard oil and soybean oil respectively (HL and HS, n=45for each group) for10weeks of diet induced obesity period. Afterward, rats in the HL and HS group weighted more than x+1.96s of LF group (DIO rats) were subdivided into two groups fed either high-fat diet continuously (HL/HL or HS/HS group) or switched to low-fat diet (HL/LF or HS/LF group) for another8weeks. Rats in control group were maintained with low-fat diet. Liver, perirenal and epididymal white adipose tissues were separated and weighed. One piece of liver was fixed with formaldehyde and used for the histology section. Fasting serum glucose, insulin, cholesterol, triglyceride and liver triglyceride content were measured and HOMA-IR was calculated.Results No significant difference was observed in the incidence of obesity, cumulative energy intake and weight gain after DIO periods between HL and HS. As expected, the HL/HL and HS/HS group exhibited increased body fat index, fasting serum insulin level, HOMA-IR, liver TG content than LF, but was increased to a greater extent in HL/HL group at the end of18th week. Both serum cholesterol, triglyceride was increased in HL/HL compared to LF and only serum cholesterol was increased in HS/HS compared to LF. Switching to low-fat-diet significantly reduced intra-abdominal fat mass, liver fat deposition, serum insulin and HOMA-IR in HL/LF and HS/LF than their counterparts continuously fed high fat diet.Conclusions High-fat-diet rich in lard oil and soybean oil showed similar ability of inducing obesity in SD rats with more deleterious in insulin resistance and hepatic steatosis of lard oil. And switching to low fat diet was confirmed to be useful in recovering from impaired insulin sensitivity and liver fat deposition in this study. It’s helpful in the prevention of obesity and related metabolic disorders. Part2Differential effects of high-fat diets enriched with lard oil or soybean oil on inflammation responseObjective To investigate the differential effects of high-fat diet enriched with lard oil or soybean oil on inflammatory markers and estimated their responses to low-fat diet intervention.Methods Establishment of animal model, grouping and intervention was as described in part1. OPN, TNF-a, TLR4and TLR2mRNA levels in frozen liver tissue were determined by Real-time PCR, protein levels of OPN in liver was determined by Western-blotting.Results HL/HL group showed increased OPN, TNF-a, TLR4and TLR2mRNA and OPN protein levels while HS/HS exhibited only higher TNF-a mRNA cepression when compared to LF group. HL/LF experienced reduced all the detected inflammatory markers and HS/LF experienced only reduced TNF-a mRNA than their counterparts continuously fed high fat diet.Conclusions Lard oil was more deleterious in insulin resistance and hepatic steatosis via promoting inflammation response in DIO rats which maybe attribute to the enrichment of saturated fatty acid (SFA). Low fat diet was confirmed to be useful in alleviating inflammation response induced by high-fat diet. Part3Differential effects of high-fat diets enriched with lard oil or soybean oil on Endoplasmic reticulum stressObjective To investigate the differential effects of high-fat diets enriched with lard oil or soybean oil on on ER stress pathways and estimated their responses to low fat diet intervention.Methods Establishment of animal model, grouping and intervention was as described in part1. BiP, PERK, CHOP, XBP1, XBPls and ATF6mRNA levels in frozen liver tissue were determined by Real-time PCR, protein levels of PERK, p-PERK, CHOP, IREla and p-IRE1α in liver were determined by Western-blotting.Results PERK pathway related markers including PERK, p-PERK, CHOP preotein and BiP, PERK, CHOP mRNA levels were sinificantlly increased in HL/HL compared to HS/HS and LF group and decreased when switchd to low-fat diet. PERK pathway related markers including PERK and p-PERK protein and PERK mRNA expressions were higher in HS/HS when copmpared to LF and switching to low-fat diet significantly reduced the PERK, p-PERK protein and PERK, CHOP, BiP mRNA expressions in HS/LF group. HL/HL and HS/HS exhibited only higher IRE1α expression and lower p-IRE1α when compared to LF group and their corresponding low-fat diet group. XBP1and XBP1s mRNA expression was similar among groups.Conclusions Lard oil was more deleterious in insulin resistance and hepatic steatosis via promoting ER stress and inflammation response in DIO rats which maybe attribute to the enrichment of saturated fatty acid (SFA). Low fat diet was confirmed to be useful in recovering from impaired insulin sensitivity and liver fat deposition in this study.