代谢性疾病中胆汁酸水平变化及相关治疗策略
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摘要
胆汁酸作为一种信号分子可以特异性地与胆汁酸受体(如法尼醇X受体、G蛋白偶联胆汁酸受体1)结合介导一系列生物调节反应。近年发现,胆汁酸在调节糖代谢、脂质代谢和能量代谢中扮演着十分重要的角色。在代谢性疾病的发生发展过程中,也常伴随着胆汁酸谱以及受体的改变。基于胆汁酸在代谢性疾病中的重要性,未来其可能成为临床诊断、预测、评价治疗效果的潜在生物标志物。该文对胆汁酸与代谢性疾病关系以及基于调节胆汁酸代谢治疗代谢性疾病进行综述。
Bile acid as a signaling molecule can specifically bind to bile acid receptors(such as farnesoid X receptor and G-protein-coupled bile acid receptor) to mediate a series of biological regulation reactions. In recent years, it has been found that bile acids are widely involved in glucose metabolism,lipid metabolism and energy metabolism. The development of metabolic diseases is usually accompanied by the changes of bile acid profiles and receptors,and thus bile acids may be applied as potential biomarkers for clinical diagnosis, prediction, and evaluation of therapeutic effects. This article reviews the relationship between bile acids and metabolic diseases, and the treatment of metabolic diseases based on the regulation of bile acid metabolism.
Bile acid as a signaling molecule can specifically bind to bile acid receptors(such as farnesoid X receptor and G-protein-coupled bile acid receptor) to mediate a series of biological regulation reactions. In recent years, it has been found that bile acids are widely involved in glucose metabolism,lipid metabolism and energy metabolism. The development of metabolic diseases is usually accompanied by the changes of bile acid profiles and receptors,and thus bile acids may be applied as potential biomarkers for clinical diagnosis, prediction, and evaluation of therapeutic effects. This article reviews the relationship between bile acids and metabolic diseases, and the treatment of metabolic diseases based on the regulation of bile acid metabolism.
引文
[1]Axelson M,Ellis E,Mork B,et al.Bile acid synthesis in cultured human hepatocytes:support for an alternative biosynthetic pathway to cholic acid[J].Hepatology,2000,31(6):1305-1312.
[2]Jia W,Xie G,Jia W.Bile acid-microbiota crosstalk in gastrointestinal inflammation and carcinogenesis[J].Nat Rev Gastroenterol Hepatol,2018,15(2):111-128.
[3]Lemoy MJ,Westworth DR,Ardeshir A,et al.Reference intervals for preprandial and postprandial serum bile acid in adult rhesus macaques(Macaca mulatta)[J].J Am Assoc Lab Anim Sci,2013,52(4):444-447.
[4]Holm R,Müllertz A,Mu H.Bile salts and their importance for drug absorption[J].Int J Pharm,2013,453(1):44-55.
[5]Joyce SA,Mac Sharry J,Casey PG,et al.Regulation of host weight gain and lipid metabolism by bacterial bile acid modification in the gut[J].Proc Natl Acad Sci U S A,2014,111(20):7421-7426.
[6]de Aguiar Vallim TQ,Tarling EJ,Edwards PA.Pleiotropic roles of bile acids in metabolism[J].Cell Metab,2013,17(5):657-669.
[7]Shi Y,Gao Y,Parys MV,et al.Definitive profiling of plasma bile acids as potential biomarkers for human liver diseases using UPLC-HRMS[J].Bioanalysis,2018,10(12):917-932.
[8]Prinz P,Hofmann T,Ahnis A,et al.Plasma bile acids show a positive correlation with body mass index and are negatively associated with cognitive restraint of eating in obese patients[J].Front Neurosci,2015,9:199.
[9]Sonne DP,van Nierop FS,Kulik W,et al.Postprandial plasma concentrations of individual bile acids and FGF-19 in patients with type 2 diabetes[J].J Clin Endocrinol Metab,2016,101(8):3002-3009.
[10]Albaugh VL,Flynn CR,Cai S,et al.Early increases in bile acids post Rouxen-Y gastric bypass are driven by insulin-sensitizing,secondary bile acids[J].JClin Endocrinol Metab,2015,100(9):E1225-E1233.
[11]Vincent RP,Omar S,Ghozlan S,et al.Higher circulating bile acid concentrations in obese patients with type 2 diabetes[J].Ann Clin Biochem,2013,50(Pt 4):360-364.
[12]Wewalka M,Patti ME,Barbato C,et al.Fasting serum taurine-conjugated bile acids are elevated in type 2 diabetes and do not change with intensification of insulin[J].J Clin Endocrinol Metab,2014,99(4):1442-1451.
[13]Ferslew BC,Xie G,Johnston CK,et al.Altered bile acid metabolome in patients with nonalcoholic steatohepatitis[J].Dig Dis Sci,2015,60(11):3318-3328.
[14]Jahnel J,Z?hrer E,Alisi A,et al.Serum bile acid levels in children with nonalcoholic fatty liver disease[J].J Pediatr Gastroenterol Nutr,2015,61(1):85-90.
[15]Puri P,Daita K,Joyce A,et al.The presence and severity of nonalcoholic steatohepatitis is associated with specific changes in circulating bile acids[J].Hepatology,2017.DOI:10.1002/hep.29359.
[16]Jiao N,Baker SS,Chapa-Rodriguez A,et al.Suppressed hepatic bile acid signalling despite elevated production of primary and secondary bile acids in NAFLD[J].Gut,2018,67(10):1881-1891.
[17]Kaur A,Patankar JV,de Haan W,et al.Loss of Cyp8b1 improves glucose homeostasis by increasing GLP-1[J].Diabetes,2015,64(4):1168-1179.
[18]Haeusler RA,Pratt-Hyatt M,Welch CL,et al.Impaired generation of12-hydroxylated bile acids links hepatic insulin signaling with dyslipidemia[J].Cell Metab,2012,15(1):65-74.
[19]Cariou B,Chetiveaux M,Za?r Y,et al.Fasting plasma chenodeoxycholic acid and cholic acid concentrations are inversely correlated with insulin sensitivity in adults[J].Nutr Metab(Lond),2011,8(1):48.
[20]Mouzaki M,Wang AY,Bandsma R,et al.Bile acids and dysbiosis in nonalcoholic fatty liver disease[J].PLo S One,2016,11(5):e0151829.
[21]Gottlieb A,Bechmann L,Canbay A.The presence and severity of nonalcoholic steatohepatitis is associated with specific changes in circulating bile acids[J].Ann Hepatol,2018,17(3):340-341.
[22]Zheng X,Huang F,Zhao A,et al.Bile acid is a significant host factor shaping the gut microbiome of diet-induced obese mice[J].BMC Biol,2017,15(1):120.
[23]Trabelsi MS,Daoudi M,Prawitt J,et al.Farnesoid X receptor inhibits glucagonlike peptide-1 production by enteroendocrine L cells[J].Nat Commun,2015,6:7629.
[24]Iuliana Ristea P,Audrey HC,Anthony L,et al.The nuclear receptor FXR is expressed in pancreaticβ-cells and protects human islets from lipotoxicity[J].FEBS Lett,2010,584(13):2845-2851.
[25]Seyer P,Vallois D,Poitry-Yamate C,et al.Hepatic glucose sensing is required to preserveβcell glucose competence[J].J Clin Invest,2013,123(4):1662-1676.
[26]Abdelkarim M,Caron S,Duhem C,et al.The farnesoid X receptor regulates adipocyte differentiation and function by promoting peroxisome proliferatoractivated receptor-γand interfering with the Wnt/β-catenin pathways[J].J Biol Chem,2010,285(47):36759-36767.
[27]Carr RM,Reid AE.FXR agonists as therapeutic agents for non-alcoholic fatty liver disease[J].Curr Atheroscler Rep,2015,17(4):500.
[28]Fuchs CD,Traussnigg SA,Trauner M.Nuclear receptor modulation for the treatment of nonalcoholic fatty liver disease[J].Semin Liver Dis,2016,36(1):69-86.
[29]Verbeke L,Mannaerts I,Schierwagen R,et al.FXR agonist obeticholic acid reduces hepatic inflammation and fibrosis in a rat model of toxic cirrhosis[J].Sci Rep,2016,6:33453.
[30]Watanabe M,Houten SM,Mataki C,et al.Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation[J].Nature,2006,439(7075):484-489.
[31]Thomas C,Gioiello A,Noriega L,et al.TGR5-mediated bile acid sensing controls glucose homeostasis[J].Cell Metab,2009,10(3):167-177.
[32]Kumar DP,Asgharpour A,Mirshahi F,et al.Activation of transmembrane bile acid receptor TGR5 modulates pancreatic isletαcells to promote glucose homeostasis[J].J Biol Chem,2016,291(13):6626-6640.
[33]Perino A,Schoonjans K.TGR5 and immunometabolism:insights from physiology and pharmacology[J].Trends Pharmacol Sci,2015,36(12):847-857.
[34]Mudaliar S,Henry RR,Sanyal AJ,et al.Efficacy and safety of the farnesoid X receptor agonist obeticholic acid in patients with type 2 diabetes and nonalcoholic fatty liver disease[J].Gastroenterology,2013,145(3):574-582.e1.
[35]Neuschwander-Tetri BA,Loomba R,Sanyal AJ,et al.Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic,non-alcoholic steatohepatitis(FLINT):a multicentre,randomised,placebo-controlled trial[J].Lancet,2015,385(9972):956-965.
[36]Chávez-Talavera O,Tailleux A,Lefebvre P,et al.Bile acid control of metabolism and inflammation in obesity,type 2 diabetes,dyslipidemia,and nonalcoholic fatty liver disease[J].Gastroenterology,2017,152(7):1679-1694.e3.
[37]Wu H,Esteve E,Tremaroli V,et al.Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes,contributing to the therapeutic effects of the drug[J].Nat Med,2017,23(7):850-858.
[38]Lee H,Ko G.Effect of metformin on metabolic improvement and gut microbiota[J].Appl Environ Microbiol,2014,80(19):5935-5943.
[39]Sun L,Xie C,Wang G,et al.Gut microbiota and intestinal FXR mediate the clinical benefits of metformin[J].Nat Med,2018,24(12):1919-1929.
[40]Fonseca VA,Handelsman Y,Staels B.Colesevelam lowers glucose and lipid levels in type 2 diabetes:the clinical evidence[J].Diabetes Obes Metab,2010,12(5):384-392.
[41]Hansen M,Sonne DP,Mikkelsen KH,et al.Bile acid sequestrants for glycemic control in patients with type 2 diabetes:a systematic review with meta-analysis of randomized controlled trials[J].J Diabetes Complications,2017,31(5):918-927.
[42]Rao A,Kosters A,Mells JE,et al.Inhibition of ileal bile acid uptake protects against nonalcoholic fatty liver disease in high-fat diet-fed mice[J].Sci Transl Med,2016,8(357):357ra122.
[43]Gawrieh S,Chalasani N.Pharmacotherapy for nonalcoholic fatty liver disease[J].Semin Liver Dis,2015,35(3):338-348.
[44]Mueller M,Thorell A,Claudel T,et al.Ursodeoxycholic acid exerts farnesoid X receptor-antagonistic effects on bile acid and lipid metabolism in morbid obesity[J].J Hepatol,2015,62(6):1398-1404.
[45]Naiara B,Lisa OZ,Haksier E,et al.Nor-ursodeoxycholic acid reverses hepatocyte-specific nemo-dependent steatohepatitis[J].Gut,2011,60(3):387-396.
[46]Gerhard GS,Styer AM,Wood GC,et al.A role for fibroblast growth factor 19and bile acids in diabetes remission after Roux-en-Y gastric bypass[J].Diabetes Care,2013,36(7):1859-1864.
[47]Steinert RE,Peterli R,Keller S,et al.Bile acids and gut peptide secretion after bariatric surgery:a 1-year prospective randomized pilot trial[J].Obesity(Silver Spring),2013,21(12):E660-E668.
[48]Dutia R,Embrey M,O'Brien CS,et al.Temporal changes in bile acid levels and 12α-hydroxylation after Roux-en-Y gastric bypass surgery in type 2diabetes[J].Int J Obes(Lond),2015,39(5):806-813.
[49]Jorgensen NB,Dirksen C,Bojsen-Moller KN,et al.Improvements in glucose metabolism early after gastric bypass surgery are not explained by increases in total bile acids and fibroblast growth factor 19 concentrations[J].J Clin Endocrinol Metab,2015,100(3):E396-E406.
[50]Jahansouz C,Xu H,Hertzel AV,et al.Bile acids increase independently from hypocaloric restriction after bariatric surgery[J].Ann Surg,2016,264(6):1022-1028.
[51]Risstad H,Kristinsson JA,Fagerland MW,et al.Bile acid profiles over 5 years after gastric bypass and duodenal switch:results from a randomized clinical trial[J].Surg Obes Relat Dis,2017,13(9):1544-1553.
[52]Khan FH,Shaw L,Zhang W,et al.Fibroblast growth factor 21 correlates with weight loss after vertical sleeve gastrectomy in adolescents[J].Obesity(Silver Spring),2016,24(11):2377-2383.
[53]Belgaumkar AP,Vincent RP,Carswell KA,et al.Changes in bile acid profile after laparoscopic sleeve gastrectomy are associated with improvements in metabolic profile and fatty liver disease[J].Obes Surg,2016,26(6):1195-1202.
[54]Lei S,Huang F,Zhao A,et al.The ratio of dihomo-γ-linolenic acid to deoxycholic acid species is a potential biomarker for the metabolic abnormalities in obesity[J].FASEB J,2017,31(9):3904-3912.
[55]Tremaroli V,Karlsson F,Werling M,et al.Roux-en-Y gastric bypass and vertical banded gastroplasty induce long-term changes on the human gut microbiome contributing to fat mass regulation[J].Cell Metab,2015,22(2):228-238.
[2]Jia W,Xie G,Jia W.Bile acid-microbiota crosstalk in gastrointestinal inflammation and carcinogenesis[J].Nat Rev Gastroenterol Hepatol,2018,15(2):111-128.
[3]Lemoy MJ,Westworth DR,Ardeshir A,et al.Reference intervals for preprandial and postprandial serum bile acid in adult rhesus macaques(Macaca mulatta)[J].J Am Assoc Lab Anim Sci,2013,52(4):444-447.
[4]Holm R,Müllertz A,Mu H.Bile salts and their importance for drug absorption[J].Int J Pharm,2013,453(1):44-55.
[5]Joyce SA,Mac Sharry J,Casey PG,et al.Regulation of host weight gain and lipid metabolism by bacterial bile acid modification in the gut[J].Proc Natl Acad Sci U S A,2014,111(20):7421-7426.
[6]de Aguiar Vallim TQ,Tarling EJ,Edwards PA.Pleiotropic roles of bile acids in metabolism[J].Cell Metab,2013,17(5):657-669.
[7]Shi Y,Gao Y,Parys MV,et al.Definitive profiling of plasma bile acids as potential biomarkers for human liver diseases using UPLC-HRMS[J].Bioanalysis,2018,10(12):917-932.
[8]Prinz P,Hofmann T,Ahnis A,et al.Plasma bile acids show a positive correlation with body mass index and are negatively associated with cognitive restraint of eating in obese patients[J].Front Neurosci,2015,9:199.
[9]Sonne DP,van Nierop FS,Kulik W,et al.Postprandial plasma concentrations of individual bile acids and FGF-19 in patients with type 2 diabetes[J].J Clin Endocrinol Metab,2016,101(8):3002-3009.
[10]Albaugh VL,Flynn CR,Cai S,et al.Early increases in bile acids post Rouxen-Y gastric bypass are driven by insulin-sensitizing,secondary bile acids[J].JClin Endocrinol Metab,2015,100(9):E1225-E1233.
[11]Vincent RP,Omar S,Ghozlan S,et al.Higher circulating bile acid concentrations in obese patients with type 2 diabetes[J].Ann Clin Biochem,2013,50(Pt 4):360-364.
[12]Wewalka M,Patti ME,Barbato C,et al.Fasting serum taurine-conjugated bile acids are elevated in type 2 diabetes and do not change with intensification of insulin[J].J Clin Endocrinol Metab,2014,99(4):1442-1451.
[13]Ferslew BC,Xie G,Johnston CK,et al.Altered bile acid metabolome in patients with nonalcoholic steatohepatitis[J].Dig Dis Sci,2015,60(11):3318-3328.
[14]Jahnel J,Z?hrer E,Alisi A,et al.Serum bile acid levels in children with nonalcoholic fatty liver disease[J].J Pediatr Gastroenterol Nutr,2015,61(1):85-90.
[15]Puri P,Daita K,Joyce A,et al.The presence and severity of nonalcoholic steatohepatitis is associated with specific changes in circulating bile acids[J].Hepatology,2017.DOI:10.1002/hep.29359.
[16]Jiao N,Baker SS,Chapa-Rodriguez A,et al.Suppressed hepatic bile acid signalling despite elevated production of primary and secondary bile acids in NAFLD[J].Gut,2018,67(10):1881-1891.
[17]Kaur A,Patankar JV,de Haan W,et al.Loss of Cyp8b1 improves glucose homeostasis by increasing GLP-1[J].Diabetes,2015,64(4):1168-1179.
[18]Haeusler RA,Pratt-Hyatt M,Welch CL,et al.Impaired generation of12-hydroxylated bile acids links hepatic insulin signaling with dyslipidemia[J].Cell Metab,2012,15(1):65-74.
[19]Cariou B,Chetiveaux M,Za?r Y,et al.Fasting plasma chenodeoxycholic acid and cholic acid concentrations are inversely correlated with insulin sensitivity in adults[J].Nutr Metab(Lond),2011,8(1):48.
[20]Mouzaki M,Wang AY,Bandsma R,et al.Bile acids and dysbiosis in nonalcoholic fatty liver disease[J].PLo S One,2016,11(5):e0151829.
[21]Gottlieb A,Bechmann L,Canbay A.The presence and severity of nonalcoholic steatohepatitis is associated with specific changes in circulating bile acids[J].Ann Hepatol,2018,17(3):340-341.
[22]Zheng X,Huang F,Zhao A,et al.Bile acid is a significant host factor shaping the gut microbiome of diet-induced obese mice[J].BMC Biol,2017,15(1):120.
[23]Trabelsi MS,Daoudi M,Prawitt J,et al.Farnesoid X receptor inhibits glucagonlike peptide-1 production by enteroendocrine L cells[J].Nat Commun,2015,6:7629.
[24]Iuliana Ristea P,Audrey HC,Anthony L,et al.The nuclear receptor FXR is expressed in pancreaticβ-cells and protects human islets from lipotoxicity[J].FEBS Lett,2010,584(13):2845-2851.
[25]Seyer P,Vallois D,Poitry-Yamate C,et al.Hepatic glucose sensing is required to preserveβcell glucose competence[J].J Clin Invest,2013,123(4):1662-1676.
[26]Abdelkarim M,Caron S,Duhem C,et al.The farnesoid X receptor regulates adipocyte differentiation and function by promoting peroxisome proliferatoractivated receptor-γand interfering with the Wnt/β-catenin pathways[J].J Biol Chem,2010,285(47):36759-36767.
[27]Carr RM,Reid AE.FXR agonists as therapeutic agents for non-alcoholic fatty liver disease[J].Curr Atheroscler Rep,2015,17(4):500.
[28]Fuchs CD,Traussnigg SA,Trauner M.Nuclear receptor modulation for the treatment of nonalcoholic fatty liver disease[J].Semin Liver Dis,2016,36(1):69-86.
[29]Verbeke L,Mannaerts I,Schierwagen R,et al.FXR agonist obeticholic acid reduces hepatic inflammation and fibrosis in a rat model of toxic cirrhosis[J].Sci Rep,2016,6:33453.
[30]Watanabe M,Houten SM,Mataki C,et al.Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation[J].Nature,2006,439(7075):484-489.
[31]Thomas C,Gioiello A,Noriega L,et al.TGR5-mediated bile acid sensing controls glucose homeostasis[J].Cell Metab,2009,10(3):167-177.
[32]Kumar DP,Asgharpour A,Mirshahi F,et al.Activation of transmembrane bile acid receptor TGR5 modulates pancreatic isletαcells to promote glucose homeostasis[J].J Biol Chem,2016,291(13):6626-6640.
[33]Perino A,Schoonjans K.TGR5 and immunometabolism:insights from physiology and pharmacology[J].Trends Pharmacol Sci,2015,36(12):847-857.
[34]Mudaliar S,Henry RR,Sanyal AJ,et al.Efficacy and safety of the farnesoid X receptor agonist obeticholic acid in patients with type 2 diabetes and nonalcoholic fatty liver disease[J].Gastroenterology,2013,145(3):574-582.e1.
[35]Neuschwander-Tetri BA,Loomba R,Sanyal AJ,et al.Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic,non-alcoholic steatohepatitis(FLINT):a multicentre,randomised,placebo-controlled trial[J].Lancet,2015,385(9972):956-965.
[36]Chávez-Talavera O,Tailleux A,Lefebvre P,et al.Bile acid control of metabolism and inflammation in obesity,type 2 diabetes,dyslipidemia,and nonalcoholic fatty liver disease[J].Gastroenterology,2017,152(7):1679-1694.e3.
[37]Wu H,Esteve E,Tremaroli V,et al.Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes,contributing to the therapeutic effects of the drug[J].Nat Med,2017,23(7):850-858.
[38]Lee H,Ko G.Effect of metformin on metabolic improvement and gut microbiota[J].Appl Environ Microbiol,2014,80(19):5935-5943.
[39]Sun L,Xie C,Wang G,et al.Gut microbiota and intestinal FXR mediate the clinical benefits of metformin[J].Nat Med,2018,24(12):1919-1929.
[40]Fonseca VA,Handelsman Y,Staels B.Colesevelam lowers glucose and lipid levels in type 2 diabetes:the clinical evidence[J].Diabetes Obes Metab,2010,12(5):384-392.
[41]Hansen M,Sonne DP,Mikkelsen KH,et al.Bile acid sequestrants for glycemic control in patients with type 2 diabetes:a systematic review with meta-analysis of randomized controlled trials[J].J Diabetes Complications,2017,31(5):918-927.
[42]Rao A,Kosters A,Mells JE,et al.Inhibition of ileal bile acid uptake protects against nonalcoholic fatty liver disease in high-fat diet-fed mice[J].Sci Transl Med,2016,8(357):357ra122.
[43]Gawrieh S,Chalasani N.Pharmacotherapy for nonalcoholic fatty liver disease[J].Semin Liver Dis,2015,35(3):338-348.
[44]Mueller M,Thorell A,Claudel T,et al.Ursodeoxycholic acid exerts farnesoid X receptor-antagonistic effects on bile acid and lipid metabolism in morbid obesity[J].J Hepatol,2015,62(6):1398-1404.
[45]Naiara B,Lisa OZ,Haksier E,et al.Nor-ursodeoxycholic acid reverses hepatocyte-specific nemo-dependent steatohepatitis[J].Gut,2011,60(3):387-396.
[46]Gerhard GS,Styer AM,Wood GC,et al.A role for fibroblast growth factor 19and bile acids in diabetes remission after Roux-en-Y gastric bypass[J].Diabetes Care,2013,36(7):1859-1864.
[47]Steinert RE,Peterli R,Keller S,et al.Bile acids and gut peptide secretion after bariatric surgery:a 1-year prospective randomized pilot trial[J].Obesity(Silver Spring),2013,21(12):E660-E668.
[48]Dutia R,Embrey M,O'Brien CS,et al.Temporal changes in bile acid levels and 12α-hydroxylation after Roux-en-Y gastric bypass surgery in type 2diabetes[J].Int J Obes(Lond),2015,39(5):806-813.
[49]Jorgensen NB,Dirksen C,Bojsen-Moller KN,et al.Improvements in glucose metabolism early after gastric bypass surgery are not explained by increases in total bile acids and fibroblast growth factor 19 concentrations[J].J Clin Endocrinol Metab,2015,100(3):E396-E406.
[50]Jahansouz C,Xu H,Hertzel AV,et al.Bile acids increase independently from hypocaloric restriction after bariatric surgery[J].Ann Surg,2016,264(6):1022-1028.
[51]Risstad H,Kristinsson JA,Fagerland MW,et al.Bile acid profiles over 5 years after gastric bypass and duodenal switch:results from a randomized clinical trial[J].Surg Obes Relat Dis,2017,13(9):1544-1553.
[52]Khan FH,Shaw L,Zhang W,et al.Fibroblast growth factor 21 correlates with weight loss after vertical sleeve gastrectomy in adolescents[J].Obesity(Silver Spring),2016,24(11):2377-2383.
[53]Belgaumkar AP,Vincent RP,Carswell KA,et al.Changes in bile acid profile after laparoscopic sleeve gastrectomy are associated with improvements in metabolic profile and fatty liver disease[J].Obes Surg,2016,26(6):1195-1202.
[54]Lei S,Huang F,Zhao A,et al.The ratio of dihomo-γ-linolenic acid to deoxycholic acid species is a potential biomarker for the metabolic abnormalities in obesity[J].FASEB J,2017,31(9):3904-3912.
[55]Tremaroli V,Karlsson F,Werling M,et al.Roux-en-Y gastric bypass and vertical banded gastroplasty induce long-term changes on the human gut microbiome contributing to fat mass regulation[J].Cell Metab,2015,22(2):228-238.