{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:21:38Z","timestamp":1792790498185,"version":"4.5.0"},"reference-count":65,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T00:00:00Z","timestamp":1700006400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Shanghai Municipal Science Commission","award":["19411971700"],"award-info":[{"award-number":["19411971700"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Imbalances in bile acid (BA) synthesis and metabolism are involved in the onset of diabetes and depression in humans and rodents. However, the role of BAs and the farnesoid X receptor (FXR)\/fibroblast growth factor (FGF) 15 signaling pathway in the development of diabetes and depression is still largely unknown. Therefore, we investigated the potential molecular mechanisms of BAs that may be associated with glucolipid metabolism disorders in diabetic mice subjected to chronic stress.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The type 2 diabetes mellitus (T2DM) mouse model was induced by feeding mice a high-fat diet and administering an intraperitoneal injection of streptozotocin (STZ). The chronic unpredictable mild stress (CUMS) procedure was performed by introducing a series of mild stressors. Forty mice were randomly divided into the regular chow feeding group and the high-fat diet feeding group. After two weeks of feeding, the mice were randomly divided into four groups: the Control group, CUMS group, T2DM group, and T2DM+CUMS group. The T2DM group and T2DM+CUMS group received an intraperitoneal injection of STZ to induce the T2DM model. The CUMS and T2DM+CUMS groups were exposed to CUMS to induce depressive-like phenotypes. Blood and tissue samples were obtained for pertinent analysis and detection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Compared with the T2DM mice, T2DM+CUMS mice had higher blood glucose and lipid levels, insulin resistance, inflammation of the liver and pancreas, impaired liver function, and increased total bile acids. These changes were accompanied by attenuated FXR signaling. Chronic stress was found to attenuate FXR expression and its downstream target, FGF15, in the ileum when compared with the T2DM group.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>FXR may play a role in the diabetic disorder of glucolipid metabolism when aggravated by chronic stress. FXR and its downstream target, FGF15, may be therapeutic targets for treating comorbid T2DM and depression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.7717\/peerj.16407","type":"journal-article","created":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T03:40:06Z","timestamp":1700019606000},"page":"e16407","source":"Crossref","is-referenced-by-count":7,"title":["Profile of the bile acid FXR-FGF15 pathway in the glucolipid metabolism disorder of diabetic mice suffering from chronic stress"],"prefix":"10.7717","volume":"11","author":[{"given":"Weijia","family":"Cai","sequence":"first","affiliation":[{"name":"Fengxian Hospital, Southern Medical University, Shanghai, China"},{"name":"School of Pharmaceutical Science, Southern Medical University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Canye","family":"Li","sequence":"additional","affiliation":[{"name":"Fengxian Hospital, Southern Medical University, Shanghai, China"},{"name":"School of Pharmaceutical Science, Southern Medical University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuanjun","family":"Su","sequence":"additional","affiliation":[{"name":"Fengxian Hospital, Southern Medical University, Shanghai, China"},{"name":"School of Pharmaceutical Science, Southern Medical University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinming","family":"Cao","sequence":"additional","affiliation":[{"name":"Fengxian Hospital, Southern Medical University, Shanghai, China"},{"name":"School of Pharmaceutical Science, Southern Medical University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhicong","family":"Chen","sequence":"additional","affiliation":[{"name":"Fengxian Hospital, Southern Medical University, Shanghai, China"},{"name":"School of Pharmaceutical Science, Southern Medical University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yitian","family":"Chen","sequence":"additional","affiliation":[{"name":"Fengxian Hospital, Southern Medical University, Shanghai, China"},{"name":"School of Pharmaceutical Science, Southern Medical University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhijun","family":"Guo","sequence":"additional","affiliation":[{"name":"Heyou Meihe Hospital, Foshan, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Cai","sequence":"additional","affiliation":[{"name":"Fengxian Mental Health Center, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Xu","sequence":"additional","affiliation":[{"name":"Fengxian Hospital, Southern Medical University, Shanghai, China"},{"name":"Sixth People\u2019 s Hospital South Campus, Shanghai Jiaotong University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4443","published-online":{"date-parts":[[2023,11,15]]},"reference":[{"key":"10.7717\/peerj.16407\/ref-1","doi-asserted-by":"publisher","first-page":"804","DOI":"10.1093\/ije\/dyr029","article-title":"Type 2 diabetes incidence and socio-economic position: a systematic review and meta-analysis","volume":"40","author":"Agardh","year":"2011","journal-title":"International Journal of Epidemiology"},{"key":"10.7717\/peerj.16407\/ref-2","doi-asserted-by":"publisher","first-page":"1854","DOI":"10.1002\/hep.29305","article-title":"Small heterodimer partner deletion prevents hepatic steatosis and when combined with farnesoid X receptor loss protects against type 2 diabetes in mice","volume":"66","author":"Akinrotimi","year":"2017","journal-title":"Hepatology"},{"key":"10.7717\/peerj.16407\/ref-3","doi-asserted-by":"publisher","first-page":"1165","DOI":"10.1111\/j.1464-5491.2006.01943.x","article-title":"The prevalence of co-morbid depression in adults with Type 2 diabetes: a systematic review and meta-analysis","volume":"23","author":"Ali","year":"2006","journal-title":"Diabetic Medicine"},{"key":"10.7717\/peerj.16407\/ref-4","doi-asserted-by":"publisher","first-page":"114561","DOI":"10.1016\/j.bcp.2021.114561","article-title":"Ganoderic acid A exerted antidepressant-like action through FXR modulated NLRP3 inflammasome and synaptic activity","volume":"188","author":"Bao","year":"2021","journal-title":"Biochemical Pharmacology"},{"key":"10.7717\/peerj.16407\/ref-5","first-page":"120","article-title":"The association between Diabetes mellitus and Depression","volume":"9","author":"B\u0103descu","year":"2016","journal-title":"The Journal of Medicine and Life"},{"key":"10.7717\/peerj.16407\/ref-6","doi-asserted-by":"publisher","first-page":"11039","DOI":"10.1074\/jbc.M510258200","article-title":"The farnesoid X receptor modulates adiposity and peripheral insulin sensitivity in mice","volume":"281","author":"Cariou","year":"2006","journal-title":"Journal of Biological Chemistry"},{"key":"10.7717\/peerj.16407\/ref-7","doi-asserted-by":"publisher","first-page":"2202","DOI":"10.1128\/MCB.01004-12","article-title":"Farnesoid X receptor inhibits the transcriptional activity of carbohydrate response element binding protein in human hepatocytes","volume":"33","author":"Caron","year":"2013","journal-title":"Molecular and Cellular Biology"},{"key":"10.7717\/peerj.16407\/ref-8","doi-asserted-by":"publisher","first-page":"773","DOI":"10.2337\/db09-9028","article-title":"Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus","volume":"58","author":"Defronzo","year":"2009","journal-title":"Diabetes"},{"key":"10.7717\/peerj.16407\/ref-9","doi-asserted-by":"publisher","first-page":"29971","DOI":"10.1074\/jbc.M501931200","article-title":"The farnesoid X receptor modulates hepatic carbohydrate metabolism during the fasting-refeeding transition","volume":"280","author":"Duran-Sandoval","year":"2005","journal-title":"Journal of Biological Chemistry"},{"key":"10.7717\/peerj.16407\/ref-10","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1016\/j.diabres.2010.01.024","article-title":"Diabetes and depression: global perspectives","volume":"87","author":"Egede","year":"2010","journal-title":"Diabetes Research and Clinical Practice"},{"key":"10.7717\/peerj.16407\/ref-11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.pcd.2021.11.001","article-title":"A systematic review and meta-analysis to compare the prevalence of depression between people with and without Type 1 and Type 2 diabetes","volume":"16","author":"Farooqi","year":"2022","journal-title":"Primary Care Diabetes"},{"key":"10.7717\/peerj.16407\/ref-12","doi-asserted-by":"publisher","first-page":"e22100","DOI":"10.1096\/fj.202101088RRR","article-title":"Co-occurrence of gut microbiota dysbiosis and bile acid metabolism alteration is associated with psychological disorders in Crohn\u2019s disease","volume":"36","author":"Feng","year":"2022","journal-title":"The FASEB Journal"},{"key":"10.7717\/peerj.16407\/ref-13","doi-asserted-by":"publisher","first-page":"104758","DOI":"10.1016\/j.neubiorev.2022.104758","article-title":"Insulin resistance in depression: a large meta-analysis of metabolic parameters and variation","volume":"139","author":"Fernandes","year":"2022","journal-title":"Neuroscience & Biobehavioral Reviews"},{"key":"10.7717\/peerj.16407\/ref-14","doi-asserted-by":"publisher","first-page":"S56","DOI":"10.1016\/s0165-0327(12)70009-5","article-title":"Co-occurrence of diabetes and depression: conceptual considerations for an emerging global health challenge","volume":"142","author":"Fisher","year":"2012","journal-title":"Journal of Affective Disorders"},{"key":"10.7717\/peerj.16407\/ref-15","doi-asserted-by":"publisher","first-page":"1096","DOI":"10.1111\/j.1464-5491.2008.02533.x","article-title":"A longitudinal study of affective and anxiety disorders, depressive affect and diabetes distress in adults with Type 2 diabetes","volume":"25","author":"Fisher","year":"2008","journal-title":"Diabetic Medicine"},{"key":"10.7717\/peerj.16407\/ref-16","doi-asserted-by":"publisher","first-page":"e78","DOI":"10.1002\/cpz1.78","article-title":"Streptozotocin-induced diabetic models in mice and rats","volume":"1","author":"Furman","year":"2021","journal-title":"Current Protocols"},{"key":"10.7717\/peerj.16407\/ref-17","doi-asserted-by":"publisher","first-page":"416254","DOI":"10.1155\/2011\/416254","article-title":"Development of a nongenetic mouse model of type 2 diabetes","volume":"2011","author":"Gilbert","year":"2011","journal-title":"Experimental Diabetes Research"},{"key":"10.7717\/peerj.16407\/ref-18","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1007\/s00213-019-05406-w","article-title":"Atorvastatin ameliorates depressive behaviors and neuroinflammatory in streptozotocin-induced diabetic mice","volume":"237","author":"Hai-Na","year":"2020","journal-title":"Psychopharmacology"},{"key":"10.7717\/peerj.16407\/ref-19","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/s00125-018-4711-2","article-title":"Global trends in diabetes complications: a review of current evidence","volume":"62","author":"Harding","year":"2019","journal-title":"Diabetologia"},{"key":"10.7717\/peerj.16407\/ref-20","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1007\/s11606-010-1272-6","article-title":"Depression in relation to long-term control of glycemial, blood pressure, and lipids in patients with diabetes","volume":"25","author":"Heckbert","year":"2010","journal-title":"Journal of General Internal Medicine"},{"key":"10.7717\/peerj.16407\/ref-21","doi-asserted-by":"publisher","first-page":"70","DOI":"10.3389\/fnbeh.2015.00070","article-title":"Deletion of mouse FXR gene disturbs multiple neurotransmitter systems and alters neurobehavior","volume":"9","author":"Huang","year":"2015","journal-title":"Frontiers in Behavioral Neuroscience"},{"key":"10.7717\/peerj.16407\/ref-22","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1039\/c4fo00843j","article-title":"Lactobacillus rhamnosus LA68 and Lactobacillus plantarum WCFS1 differently influence metabolic and immunological parameters in high fat diet-induced hypercholesterolemia and hepatic steatosis","volume":"6","author":"Ivanovic","year":"2015","journal-title":"Food & Function"},{"key":"10.7717\/peerj.16407\/ref-23","doi-asserted-by":"publisher","first-page":"2953","DOI":"10.3892\/mmr.2019.9915","article-title":"Regulation of Fgf15 expression in the intestine by glucocorticoid receptor","volume":"19","author":"Jia","year":"2019","journal-title":"Molecular Medicine Reports"},{"key":"10.7717\/peerj.16407\/ref-24","doi-asserted-by":"publisher","first-page":"1621","DOI":"10.1126\/science.1198363","article-title":"FGF19 as a postprandial, insulin-independent activator of hepatic protein and glycogen synthesis","volume":"331","author":"Kir","year":"2011","journal-title":"Science"},{"issue":"6","key":"10.7717\/peerj.16407\/ref-25","doi-asserted-by":"publisher","first-page":"232","DOI":"10.3390\/biom9060232","article-title":"The biosynthesis, signaling, and neurological functions of bile acids","volume":"9","author":"Kiriyama","year":"2019","journal-title":"Biomolecules"},{"key":"10.7717\/peerj.16407\/ref-26","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1159\/000371670","article-title":"Bile acids as hormones: the FXR-FGF15\/19 pathway","volume":"33","author":"Kliewer","year":"2015","journal-title":"Digestive Diseases"},{"key":"10.7717\/peerj.16407\/ref-27","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1370\/afm.423","article-title":"Effects of enhanced depression treatment on diabetes self-care","volume":"4","author":"Lin","year":"2006","journal-title":"Annals of Family Medicine"},{"key":"10.7717\/peerj.16407\/ref-28","doi-asserted-by":"publisher","first-page":"e2100324","DOI":"10.1002\/pmic.202100324","article-title":"The clinical and mechanistic roles of bile acids in depression. Alzheimer\u2019s disease, and stroke","volume":"22","author":"Lirong","year":"2022","journal-title":"Proteomics"},{"key":"10.7717\/peerj.16407\/ref-29","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1016\/s0026-0495(98)90027-0","article-title":"Nongenetic mouse models of non-insulin-dependent diabetes mellitus","volume":"47","author":"Luo","year":"1998","journal-title":"Metabolism"},{"key":"10.7717\/peerj.16407\/ref-30","doi-asserted-by":"publisher","first-page":"1102","DOI":"10.1172\/JCI25604","article-title":"Farnesoid X receptor is essential for normal glucose homeostasis","volume":"116","author":"Ma","year":"2006","journal-title":"Journal of Clinical Investigation"},{"key":"10.7717\/peerj.16407\/ref-31","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.1002\/jcsm.12887","article-title":"Nampt activator P7C3 ameliorates diabetes and improves skeletal muscle function modulating Cell Metabolismolism and lipid mediators","volume":"13","author":"Manickam","year":"2022","journal-title":"Journal of Cachexia, Sarcopenia and Muscle"},{"key":"10.7717\/peerj.16407\/ref-32","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.mce.2012.05.004","article-title":"FXR signaling in the enterohepatic system","volume":"368","author":"Matsubara","year":"2013","journal-title":"Molecular and Cellular Endocrinology"},{"key":"10.7717\/peerj.16407\/ref-33","doi-asserted-by":"publisher","first-page":"617","DOI":"10.3389\/fnins.2017.00617","article-title":"Bile acid signaling pathways from the enterohepatic circulation to the central nervous system","volume":"11","author":"Mertens","year":"2017","journal-title":"Frontiers in Neuroscience"},{"key":"10.7717\/peerj.16407\/ref-34","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1007\/s12017-020-08625-z","article-title":"Bile acids: a communication channel in the gut-brain axis","volume":"23","author":"Monteiro-Cardoso","year":"2021","journal-title":"NeuroMolecular Medicine"},{"key":"10.7717\/peerj.16407\/ref-35","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1016\/S2213-8587(15)00134-5","article-title":"The link between depression and diabetes: the search for shared mechanisms","volume":"3","author":"Moulton","year":"2015","journal-title":"The Lancet Diabetes & Endocrinology"},{"key":"10.7717\/peerj.16407\/ref-36","doi-asserted-by":"publisher","first-page":"e208","DOI":"10.1002\/cpz1.208","article-title":"Models of Depression: Unpredictable Chronic Mild Stress in Mice","volume":"1","author":"Nollet","year":"2021","journal-title":"Current Protocols"},{"key":"10.7717\/peerj.16407\/ref-37","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.tem.2014.10.002","article-title":"Tissue-specific actions of the metabolic hormones FGF15\/19 and FGF21","volume":"26","author":"Owen","year":"2015","journal-title":"Trends in Endocrinology & Metabolism"},{"key":"10.7717\/peerj.16407\/ref-38","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1038\/s42255-022-00559-z","article-title":"Metabolic Messengers: bile acids","volume":"4","author":"Perino","year":"2022","journal-title":"Nature Metabolism"},{"key":"10.7717\/peerj.16407\/ref-39","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1016\/S2213-8587(15)00045-5","article-title":"Depression and diabetes: treatment and health-care delivery","volume":"3","author":"Petrak","year":"2015","journal-title":"The Lancet Diabetes & Endocrinology"},{"key":"10.7717\/peerj.16407\/ref-40","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1210\/me.2002-0120","article-title":"Bile acids induce the expression of the human peroxisome proliferator-activated receptor alpha gene via activation of the farnesoid X receptor","volume":"17","author":"Pineda Torra","year":"2003","journal-title":"Molecular Endocrinology"},{"key":"10.7717\/peerj.16407\/ref-41","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1007\/s00335-013-9456-0","article-title":"High-fat feeding rapidly induces obesity and lipid derangements in C57BL\/6N mice","volume":"24","author":"Podrini","year":"2013","journal-title":"Mammalian Genome"},{"key":"10.7717\/peerj.16407\/ref-42","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1159\/000521515","article-title":"Early insulin resistance, type 2 diabetes, and treatment options in childhood","volume":"95","author":"Polidori","year":"2022","journal-title":"Hormone Research in Paediatrics"},{"key":"10.7717\/peerj.16407\/ref-43","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1016\/j.cmet.2011.03.019","article-title":"FGF15\/19 regulates hepatic glucose metabolism by inhibiting the CREB-PGC-1 \u03b1 pathway","volume":"13","author":"Potthoff","year":"2011","journal-title":"Cell Metabolism"},{"key":"10.7717\/peerj.16407\/ref-44","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1101\/gad.184788.111","article-title":"Endocrine fibroblast growth factors 15\/19 and 21: from feast to famine","volume":"26","author":"Potthoff","year":"2012","journal-title":"Genes & Development"},{"issue":"12","key":"10.7717\/peerj.16407\/ref-45","doi-asserted-by":"publisher","first-page":"3984","DOI":"10.3390\/ijms19123984","article-title":"UPLC-Q\/TOF-MS-based serum metabolomics reveals hypoglycemic effects of rehmannia glutinosa, coptis chinensis and their combination on high-fat-diet-induced diabetes in KK-Ay mice","volume":"19","author":"Qin","year":"2018","journal-title":"International Journal of Molecular Sciences"},{"key":"10.7717\/peerj.16407\/ref-46","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1152\/physrev.00008.2017","article-title":"Pancreatic \u03b2-cell electrical activity and insulin secretion: of mice and men","volume":"98","author":"Rorsman","year":"2018","journal-title":"Physiological Reviews"},{"key":"10.7717\/peerj.16407\/ref-47","doi-asserted-by":"publisher","first-page":"47","DOI":"10.31887\/DCNS.2018.20.1\/nsartorius","article-title":"Depression and diabetes","volume":"20","author":"Sartorius","year":"2018","journal-title":"Dialogues in Clinical Neuroscience"},{"key":"10.7717\/peerj.16407\/ref-48","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1097\/MCO.0b013e3283547171","article-title":"Role of fibroblast growth factor 19 in the control of glucose homeostasis","volume":"15","author":"Schaap","year":"2012","journal-title":"Current Opinion in Clinical Nutrition & Metabolic Care"},{"key":"10.7717\/peerj.16407\/ref-49","doi-asserted-by":"publisher","first-page":"1133","DOI":"10.1111\/liv.12456","article-title":"Protective effects of farnesoid X receptor (FXR) on hepatic lipid accumulation are mediated by hepatic FXR and independent of intestinal FGF15 signal","volume":"35","author":"Schmitt","year":"2015","journal-title":"Liver International"},{"key":"10.7717\/peerj.16407\/ref-50","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1007\/s40265-015-0347-4","article-title":"Depression in type 2 diabetes mellitus: prevalence, impact, and treatment","volume":"75","author":"Semenkovich","year":"2015","journal-title":"Drugs"},{"key":"10.7717\/peerj.16407\/ref-51","doi-asserted-by":"publisher","first-page":"e92574","DOI":"10.1371\/journal.pone.0092574","article-title":"Multiple low-dose radiation prevents type 2 diabetes-induced renal damage through attenuation of dyslipidemia and insulin resistance and subsequent renal inflammation and oxidative stress","volume":"9","author":"Shao","year":"2014","journal-title":"PLOS ONE"},{"key":"10.7717\/peerj.16407\/ref-52","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1016\/s0092-8674(00)00062-3","article-title":"Targeted disruption of the nuclear receptor FXR\/BAR impairs bile acid and lipid homeostasis","volume":"102","author":"Sinal","year":"2000","journal-title":"Cell"},{"key":"10.7717\/peerj.16407\/ref-53","doi-asserted-by":"publisher","first-page":"3002","DOI":"10.1210\/jc.2016-1607","article-title":"Postprandial plasma concentrations of individual bile acids and FGF-19 in patients with type 2 diabetes","volume":"101","author":"Sonne","year":"2016","journal-title":"The Journal of Clinical Endocrinology and Metabolism"},{"key":"10.7717\/peerj.16407\/ref-54","doi-asserted-by":"publisher","first-page":"109119","DOI":"10.1016\/j.diabres.2021.109119","article-title":"IDF Diabetes Atlas: global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045","volume":"183","author":"Sun","year":"2022","journal-title":"Diabetes Research and Clinical Practice"},{"key":"10.7717\/peerj.16407\/ref-55","doi-asserted-by":"publisher","first-page":"1919","DOI":"10.1038\/s41591-018-0222-4","article-title":"Gut microbiota and intestinal FXR mediate the clinical benefits of metformin","volume":"24","author":"Sun","year":"2018","journal-title":"Nature Medicine"},{"key":"10.7717\/peerj.16407\/ref-56","doi-asserted-by":"publisher","first-page":"e2778","DOI":"10.1097\/MD.0000000000002778","article-title":"Insulin resistance is associated with total bile acid level in type 2 diabetic and nondiabetic population: a cross-sectional study","volume":"95","author":"Sun","year":"2016","journal-title":"Medicine"},{"key":"10.7717\/peerj.16407\/ref-57","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1002\/wps.20309","article-title":"Diabetes mellitus in people with schizophrenia, bipolar disorder and major depressive disorder: a systematic review and large scale meta-analysis","volume":"15","author":"Vancampfort","year":"2016","journal-title":"World Psychiatry"},{"key":"10.7717\/peerj.16407\/ref-58","doi-asserted-by":"publisher","first-page":"110","DOI":"10.2174\/1570161117666190405165151","article-title":"Macrovascular complications of type 2 diabetes mellitus","volume":"18","author":"Viigimaa","year":"2020","journal-title":"Current Vascular Pharmacology"},{"key":"10.7717\/peerj.16407\/ref-59","doi-asserted-by":"publisher","first-page":"1408","DOI":"10.1172\/jci21025","article-title":"Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c","volume":"113","author":"Watanabe","year":"2004","journal-title":"Journal of Clinical Investigation"},{"key":"10.7717\/peerj.16407\/ref-60","doi-asserted-by":"publisher","first-page":"1408","DOI":"10.1172\/jci21025","article-title":"Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c","volume":"113","author":"Watanabe","year":"2004","journal-title":"Journal of Clinical Investigation"},{"key":"10.7717\/peerj.16407\/ref-61","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1016\/j.neuropharm.2017.11.038","article-title":"Insulin resistance, an unmasked culprit in depressive disorders: promises for interventions","volume":"136","author":"Watson","year":"2018","journal-title":"Neuropharmacology"},{"key":"10.7717\/peerj.16407\/ref-62","doi-asserted-by":"publisher","first-page":"107867","DOI":"10.1016\/j.pharmthera.2021.107867","article-title":"The pathophysiological function of non-gastrointestinal farnesoid X receptor","volume":"226","author":"Yan","year":"2021","journal-title":"Pharmacology & Therapeutics"},{"key":"10.7717\/peerj.16407\/ref-63","doi-asserted-by":"publisher","first-page":"852","DOI":"10.1039\/b914751a","article-title":"Metabonomics study of urine and plasma in depression and excess fatigue rats by ultra fast liquid chromatography coupled with ion trap-time of flight mass spectrometry","volume":"6","author":"Zhang","year":"2010","journal-title":"Molecular BioSystems"},{"key":"10.7717\/peerj.16407\/ref-64","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.1073\/pnas.0506982103","article-title":"Activation of the nuclear receptor FXR improves hyperglycemia and hyperlipidemia in diabetic mice","volume":"103","author":"Zhang","year":"2006","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"10.7717\/peerj.16407\/ref-65","doi-asserted-by":"publisher","first-page":"112832","DOI":"10.1016\/j.jep.2020.112832","article-title":"Metabolomics analysis of the antidepressant prescription Danzhi Xiaoyao Powder in a rat model of Chronic Unpredictable Mild Stress (CUMS)","volume":"260","author":"Zhu","year":"2020","journal-title":"Journal of Ethnopharmacology"}],"container-title":["PeerJ"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/peerj.com\/articles\/16407.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/16407.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/16407.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/16407.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T03:40:17Z","timestamp":1700019617000},"score":1,"resource":{"primary":{"URL":"https:\/\/peerj.com\/articles\/16407"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,15]]},"references-count":65,"alternative-id":["10.7717\/peerj.16407"],"URL":"https:\/\/doi.org\/10.7717\/peerj.16407","archive":["CLOCKSS","LOCKSS","Portico"],"relation":{},"ISSN":["2167-8359"],"issn-type":[{"value":"2167-8359","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,15]]},"article-number":"e16407"}}