| The production of high-quality pork is an important issue that restricts the stable development of modern animal husbandry.Exploring the regulatory mechanism of pig fat deposition is an effective way to improve pork quality.In recent years,the regulation of glucose and lipid metabolism homeostasis by bile acids has gradually been emphasized.Studies have shown that there is a unique bile acid in pigs,collectively known as hyocholic acid(HCAs).HCAs are different from bile acids found in humans and rodents,and their types and contents differ significantly.Trimethylamine oxide(TMAO)is a secondary metabolite produced by the gut microbiota.Studies have shown that low-dose TMAO has a certain promoting effect on bile acid metabolism and can promote cholesterol transport and fat metabolism in the body.However,the synergistic effect of TMAO with porcine bile acid and its mechanism are still unclear.This article focuses on a high-fat diet induced obesity mouse model,pig intestinal epithelial cells,and liver cells.Using techniques such as q PCR,Western blot,and Elisa,we investigate the effects of co treatment of HCAs and TMAO on fat metabolism in the intestine and liver,as well as the regulation of lipid metabolism homeostasis.The research results can provide new strategies for improving the quality of animal products and reducing excessive fat deposition in obese animals.The main research findings are as follows:1.The co treatment of HCAs and TMAO improves the symptoms of lipid metabolism disorders in obese mice.The co treatment of HCAs and TMAO can improve the physiological phenotype of obese mice,resulting in a significant weight loss(p<0.01).It also has an impact on the liver weight and fat weight of obese mice,with the greatest impact on subcutaneous fat content,with a significant weight decrease(p<0.01);It has a certain impact on the blood lipid content in peripheral serum,with a significant decrease in TG,TC,and LDL-C content and an increase in HDL-C content(p<0.01);By detecting the content of inflammatory factors in peripheral blood,the results showed that the inflammatory factors IL-6 and IL-1 in serum β、 MCP-1、TNF-α The degree of decrease in the content of all reached a significant level(p<0.05);The changes in the content of lipid metabolism related enzymes LPL and HL in serum indicate that co treatment with HCAs and TMAO has a significant impact on the changes of related enzymes in the body(p<0.01),which accelerates the speed of fat metabolism in the body;In addition,the significant increase in free fatty acids in pig intestinal cell culture medium can be determined(p<0.01),indicating that lipolysis in cells is accelerating.These results indicate that co treatment with HCAs and TMAO significantly alleviates the symptoms of lipid metabolism disorders in obese animals.2.HCAs co treated with TMAO regulate lipid metabolism homeostasis in the intestine through FXR-FG19-NPC1L1.The co treatment of HCA and TMAO has significant regulation on lipid metabolism disorders in the intestine.For the intestinal wall injury caused by obesity,it can be seen from the HE staining section that the co treatment of HCA and TMAO alleviated this injury and significantly inhibited the m RNA expression of lipid transport related genes FATP4,CD36,NPC1L1,and Numb in the intestine(p<0.01);Similarly,we tested the content of inflammatory factors in the intestine and the results showed a significant decrease in the content of inflammatory factors(p<0.05);To further investigate the regulatory mechanisms,we detected FXR,FGF19,and their downstream secreted protein NPC1L1 in the intestine.The m RNA and protein immunoblotting results showed that co treatment with HCA and TMAO significantly activated FXR receptors in the intestine,and significantly upregulated FGF19,which had a significant regulatory effect on the increase in NPC1L1 secretion(p<0.01).Next,we examined the lipid synthesis genes ACC,FAS,and The m RNA expression levels of CPT1 and lipolysis gene ATGL were detected,and the results showed that the liposynthesis gene was significantly downregulated while the lipolysis gene was significantly upregulated(p<0.05);The detection results of genes related to lipid metabolism have the same trend as those in pig intestinal cells.The above results demonstrate that the co treatment of HCA and TMAO regulates lipid metabolism in the intestine through FXR-FGF19-NPC1L1.3.Co treatment of HCAs and TMAO in liver tissue via PPAR α-The SREBP-1pathway interferes with lipid metabolism disorders in the body.The content of glutamic grass transaminase and glutamic pyruvic transaminase was detected.The results showed that the liver of obese mice had obvious liver injury,and the co treatment of HCA and TMAO alleviated the liver injury(p<0.01);From the HE staining sections of the liver,it can be seen that co treatment with HCA and TMAO also slowed down the fatty liver situation in obese mice;The detection of inflammatory factor content in the liver showed that co treatment with HCA and TMAO slowed down the inflammatory response in the liver(p<0.01);We further investigated the pathway of co treatment of HCA and TMAO in regulating lipid metabolism in the liver.From the results,it can be seen that co treatment of HCA and TMAO activates PPAR through FXR α Furthermore,it inhibits the expression of SREBP-1,achieving the goal of de novo inhibition of fat synthesis;The downregulation of lipid synthesis genes and upregulation of lipolysis genes in obese mice and pig liver cell lines were extremely significant(p<0.01).The above results show that the co treatment of HCAs and TMAO in liver tissue through PPAR α-The SREBP-1 pathway regulates lipid metabolism.In summary,under the co existence of porcine bile acids(HCAs)and low-dose TMAO,there is a significant regulatory effect on lipid metabolism in obese animals.In intestinal tissue,lipid absorption and transport are mainly inhibited through the FXR-FG19-NPC1L1 pathway,while in liver tissue,they are inhibited through PPAR α-SREBP-1 pathway inhibits De novo synthesis of fat.Although the pathways regulating lipid metabolism are different in different tissues,they all play a role in inhibiting lipid synthesis and promoting lipid decomposition.This plays an indispensable role in reducing subcutaneous fat deposition in obese animals and improving the quality of livestock and poultry products. |
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