Bile Acid Recognition by Mouse Ileal Bile Acid Binding Protein

et al. 2018

Nutr Metab (Lond)

BackgroundBile acids play a pivotal role in cholesterol metabolism via the enterohepatic circulation. This study investigated the effects of medium-chain triglycerides (MCTs)/medium-chain fatty acids (MCFAs) on the reduction of bile acid absorption in the small intestine and the mechanisms of action in vivo and partially verified in vitro.MethodsThirty-six C57BL/6 J mice with hypercholesterolaemia were randomly divided into 3 groups: fed a cholesterol-rich diet (CR group), fed a cholesterol-rich and medium-chain triglyceride diet (CR-MCT group) and fed a cholesterol-rich and long-chain triglyceride diet (CR-LCT group). Body weights and blood lipid profiles were measured in all groups after 16 weeks of treatment. The concentrations of bile acids in bile and faeces were analysed using HPLC-MS (high-performance liquid chromatography-mass spectrometry). Gene transcription and the expression levels associated with bile acid absorption in the small intestines were determined using real-time PCR and Western blot. Ileal bile acid binding protein (I-BABP) was analysed using immunofluorescence. The effects of MCFAs on the permeability of bile acid (cholic acid, CA) in Caco-2 cell monolayers and I-BABP expression levels in Caco-2 cells treated with caprylic acid (C8:0), capric acid (C10:0), stearic acid (C18:0) and oleic acid (C18:1) were determined.ResultsMice in the CR-MCT group exhibited lower body weights and serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels and a higher HDL-C/LDL-C ratio than the CR-LCT group (P < 0.05). The concentrations of primary bile acids (primarily CA) and secondary bile acids in faeces and secondary bile acids in bile in the CR-MCT group were significantly higher than in the CR-LCT group (P < 0.05). C8:0 and C10:0 decreased the permeability of CA in Caco-2 cell monolayers. MCT/MCFAs (C8:0 and C10:0) inhibited I-BABP gene expression in the small intestines and Caco-2 cells (P < 0.05).ConclusionsMCT slowed the body weight increase and promoted the excretion of bile acids. MCT lowered serum cholesterol levels at least partially via reduction of bile acid absorption in the small intestine by inhibition of I-BABP expression. Our results provide the basis for clinical trials of MCT as a dietary supplement for lowering plasma cholesterol and reducing risk of CHD.

Section: Discussionmentioning

confidence: 99%

Medium-chain fatty acids decrease serum cholesterol via reduction of intestinal bile acid reabsorption in C57BL/6J mice

Liu

et al. 2018

Nutr Metab (Lond)

“…Although FABPs share a highly conserved structure, each of them has its own sequence and exhibits distinct affinity for ligand preferences [16]. Specifically, ilealtype FABP that located in the distal portion of small intestine is regarded as the cytosolic receptor for bile acids, although it has a low binding affinity for fatty acids [17]. Therefore, the reduced expression of FABP6 with the resultant downregulations of GO clusters of transport and transporter activity might suggest a compromised reabsorption of luminal bile acids into enterocytes [17], resulting in a disordered regulation of lipid metabolism of the layers in LP group.…”

Section: Discussionmentioning

confidence: 99%

“…Specifically, ilealtype FABP that located in the distal portion of small intestine is regarded as the cytosolic receptor for bile acids, although it has a low binding affinity for fatty acids [17]. Therefore, the reduced expression of FABP6 with the resultant downregulations of GO clusters of transport and transporter activity might suggest a compromised reabsorption of luminal bile acids into enterocytes [17], resulting in a disordered regulation of lipid metabolism of the layers in LP group. On the other hand, the decreased expression of FABP1, FABP2 and FABP3 with the relevant downregulation of GO cluster of lipid binding were deduced to induce a malabsorption of fatty acids in LP group, since the entry of them from the lumen across the apical side of enterocytes was highly dependent on the binding by FABPs [18].…”

Section: Discussionmentioning

confidence: 99%

Transcriptome Analysis Reveals Mechanism Underlying the Differential Intestinal Functionality of Laying Hens in the Late Phase and Peak Phase of Production

Wang

et al. 2019

Preprint

Background The compromised performance of laying hens in the late phase of production relative to the peak production was thought to be associated with the impairment of intestinal functionality, which plays essential roles in contributing to their overall health and production performance. In the present study, RNA sequencing was used to investigate differences in the expression profile of intestinal functionality-related genes and associated pathways between layers in the late phase and peak phase of production.Results A total of 104 upregulated genes with 190 downregulated genes were identified in the ileum of layers in the late phase of production compared to those at peak production. These upregulated genes were found to be enriched in little KEGG pathway, however, the downregulated genes were enriched in the pathways of PPAR signaling pathway, oxidative phosphorylation and glutathione metabolism. Besides, these downregulated genes were mapped to several GO clusters in relation to lipid metabolism, electron transport of respiratory chain, and oxidation resistance. Similarly, there were lower activities of total superoxide dismutase, glutathione S-transferase and Na+/K+-ATPase, and reductions of total antioxidant capacity and ATP level, along with an elevation in malondialdehyde content in the ileum of layers in the late phase of production as compared with those at peak production.Conclusions The intestine of layers in the late phase of production were predominantly characterized by a disorder of lipid metabolism, concurrent with impairments of energy production and antioxidant property. This study uncovers the mechanism underlying differences between the intestinal functionality of layers in the late phase and peak phase of production, thereby providing potential targets for the genetic control or dietary modulation of intestinal hypofunction of layers in the late phase of production. BackgroundLayer industry is one of the key components contributing to sustainable food sources in the world.

“…Although FABPs share a highly conserved structure, each of them has its own sequence and exhibits distinct affinity for ligand preferences [25]. Specifically, ilealtype FABP that located in the distal small intestine is regarded as the cytosolic receptor for bile acids, although it has a low binding affinity for fatty acids [26]. Therefore, the reduced expression of FABP6 with the resultant downregulations of GO clusters of transport and transporter activity might suggest a compromised reabsorption of luminal bile acids into enterocytes [26], resulting in a disordered regulation of lipid metabolism of the laying hens in LP group.…”

Section: Discussionmentioning

confidence: 99%

“…Specifically, ilealtype FABP that located in the distal small intestine is regarded as the cytosolic receptor for bile acids, although it has a low binding affinity for fatty acids [26]. Therefore, the reduced expression of FABP6 with the resultant downregulations of GO clusters of transport and transporter activity might suggest a compromised reabsorption of luminal bile acids into enterocytes [26], resulting in a disordered regulation of lipid metabolism of the laying hens in LP group. On the other hand, the decreased expression of FABP1, FABP2 and FABP3 with the relevant downregulation of GO cluster of lipid binding were deduced to induce a malabsorption of fatty acids in LP group, since the entry of them from the lumen across the apical side of enterocytes was highly dependent on the binding by FABPs [27].…”

Section: Discussionmentioning

confidence: 99%

Transcriptome Analysis Reveals Mechanism Underlying the Differential Intestinal Functionality of Laying Hens in the Late Phase and Peak Phase of Production

Wang

et al. 2019

Preprint

Background: The compromised performance of laying hens in the late phase of production relative to the peak production was thought to be associated with the impairment of intestinal functionality, which plays essential roles in contributing to their overall health and production performance. In the present study, RNA sequencing was used to investigate differences in the expression profile of intestinal functionality-related genes and associated pathways between laying hens in the late phase and peak phase of production. Results : A total of 104 upregulated genes with 190 downregulated genes were identified in the ileum (the distal small intestine) of laying hens in the late phase of production compared to those at peak production. These upregulated genes were found to be enriched in little KEGG pathway, however, the downregulated genes were enriched in the pathways of PPAR signaling pathway, oxidative phosphorylation and glutathione metabolism. Besides, these downregulated genes were mapped to several GO clusters in relation to lipid metabolism, electron transport of respiratory chain, and oxidation resistance. Similarly, there were lower activities of total superoxide dismutase, glutathione S-transferase and Na + /K + -ATPase, and reductions of total antioxidant capacity and ATP level, along with an elevation in malondialdehyde content in the ileum of laying hens in the late phase of production as compared with those at peak production. Conclusions: The intestine of laying hens in the late phase of production were predominantly characterized by a disorder of lipid metabolism, concurrent with impairments of energy production and antioxidant property. This study uncovers the mechanism underlying differences between the intestinal functionality of laying hens in the late phase and peak phase of production, thereby providing potential targets for the genetic control or dietary modulation of intestinal hypofunction of laying hens in the late phase of production.