Perturbation Of Lipid Metabolism By Long-Term Low-Dose Cadmium Exposure In Cyprinus Carpio

Common carp is one of the main commercial fishes in China.Recent years,with the frequent occurrence of water pollution events,the yield and quality of common carp have been greatly affected.Cadmium(Cd)is a kind of heavy metal with strong bioaccumulation,high toxicity and wide distribution,which is one of the main pollutants leading to water pollution.Waterborne Cd pollution not only affects the growth and development of the fish,but also poses threat to the food safety and public health.Lipids are the crucial nutrients for fish to maintain life activities.The liver is not only the main organ of lipid synthesis and metabolism,but also the target organ of Cd exposure.Therefore,in our study,common carp was selected as the research object and long-term low-dose Cd exposure was selected to simulate the real environment.By clarifying the effects of Cd on the morphological characteristics,liver function and lipid metabolism of common carp and further exploring the molecular mechanism of Cd toxicity in water to the liver of common carp,it provides scientific basis for the study of Cd poisoning and water pollution monitoring,and also provides reference for promoting the healthy development of China’s aquaculture industry.The main results are as follows: 1.The effects of Cd exposure on physical indicators and hepatoxicityBased on the upper limit of Cd concentration of 0.005 mg/L in China’s fishery aquaculture water quality standards,our study set up two treatment groups(0.005 mg/L,0.05 mg/L,hereinafter referred to as low concentration group and high concentration group)and a control group.After 60 days of Cd exposure in water,through calculating the physical indicators of common carp,we found that the visceral index and hepatic index increased with the increase of Cd concentration.The result suggested that the body may have lipid deposition.The accumulation of Cd in the liver showed a dose effect with the exposure concentration of Cd.At the same time,the concentration of ALT and AST in serum also increased with the increase of dose,which showed that liver function has been damaged to a certain extent.And the content of H2O2 and MDA in the liver of the exposed group increased,which suggested that the oxidative damage caused by the accumulation of Cd in the liver may be the main cause of liver damage.Observing the liver tissue structure,we found that low concentration of Cd had no significant effect on the structure of the liver,while high concentration of Cd can cause slight inflammatory cell infiltration in liver tissue.The above results indicated that long-term low-dose Cd exposure may cause lipid deposition in the body,Although Cd exposure does not significantly change the liver tissue structure,and the oxidative damage caused by the accumulation of Cd still had a certain degree of damage to the liver.2.The effects of Cd exposure on biochemical indexes related to lipid metabolismThrough detecting biochemical indicators of lipid metabolism in serum and liver,the results showed that TG was elevated in serum and TG decreased in the liver.It suggested that the molecules involved in TG synthesis,transport and decomposition may play a role in this process in the liver.The change of CHO was opposite to TG,which were that the CHO decreased in serum and the CHO increased in the liver.It showed that the molecules involved in CHO synthesis,transport and decomposition play a role in the liver.The oil-Red O staining and cholesterol staining confirmed the above-mentioned changes of TG and CHO in the liver,with decreased the number and size of lipid droplets and increased CHO accumulation.The results of Soxhlet extraction also confirmed that the content of crude lipid increased in the liver and had a dose effect.The above results indicated that long-term low-dose Cd exposure led to disorders of hepatic lipid metabolism.The increase of CHO content contributed to the elevation of crude lipid content in the liver.3.The potential molecular mechanism responsible for disordered lipid metabolism after Cd exposureBy measuring the liver antioxidant-related genes,the liver antioxidant genes Nrf2 and HO-1 were decreased,and the antioxidant effect of the body was weakened,resulting in liver peroxidation damage.Through the genes associated with liverlipid metabolism in the liver,we found that when in the case of Cd exposure in the high-dosegroup,TG synthetic related genes(HNF-4α,PPARγ,SREBP-1c,SCD1,FAS,CD36)decreased significantly,TG synthesis decreased in the liver.Apo B100 was significantly increased in the low-dose group,Apo B100 and MTTP were significantly increased in the high-dose group,indicating that the role of the liver exoblastic TG was enhanced.Involved in fatty acid β-oxidation-related genes(CPT-1,VLCAD,SCAD,LCAD and ACOX1)were significantly increased,and FAA was consumed by oxidation,resulting in a decrease in FAA for synthetic TG raw materials and a decrease in liver TG content.These results further explained the reason for the decline of TG in the liver.By measuring genes related to cholesterol metabolism in liver,the results showed that HMGCR,the main synthetic enzyme of CHO,significantly increased,indicating an increase in liver CHO synthesis.With the increase of Cd concentration,CHO exfflux protein ABCA1,ABCG1,ABCG5,ABCG8 and OSBP significantly decreased,indicating that liver CHO exfflux decreased and resulting in an increase in the retention of CHO in the liver.The main gene for CHO breaking-down,the expression of CYP7A1 was decreased,although there was no significant difference.This indicated that the decomposition of CHO in the liver is reduced.These results explained the increased CHO content in the liver.Combined with the results in previous chapter,we provided a possible molecular mechanism for the increase of crude lipid content in the liver.