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Lee SY. Jejunoileal side-to-side anastomosis as a promising option for type 2 diabetes. World J Diabetes 2025; 16:103546. [DOI: 10.4239/wjd.v16.i4.103546] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2024] [Revised: 01/20/2025] [Accepted: 02/07/2025] [Indexed: 02/28/2025] Open
Abstract
In this editorial, I discuss the article by Wang et al, published in the World Journal of Diabetes, which explores jejunoileal side-to-side anastomosis as a novel surgical intervention for type 2 diabetes mellitus (T2DM). T2DM, often associated with obesity, remains a global health challenge, as sustained remission is difficult to achieve with conventional pharmacological therapy. Jejunoileal anastomosis offers a promising alternative, particularly for patients with normal or relatively high body mass index, and addresses the unique challenges posed by diverse patient populations. This procedure preserves gastric anatomy while simultaneously improving metabolic parameters, such as glycemic control, lipid profiles, and pancreatic β-cell function. Unlike traditional metabolic surgeries that involve permanent anatomical alterations, this approach provides advantages such as reversibility, shorter operative times, and minimal nutritional complications, making it appealing to patients for whom conventional bariatric surgery is unsuitable. Advances in gut hormone physiology and incretin modulation support these findings. This innovative approach represents a potential paradigm shift in T2DM treatment, offering insights into the evolving role of surgical interventions in metabolic regulation. While early findings show promising diabetes remission rates and metabolic improvements at six months post-surgery, further studies with longer follow-up periods and broader patient cohorts are required.
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Affiliation(s)
- Sang Yeoup Lee
- Family Medicine and Biomedical Research Institute, Pusan National University Yangsan Hospital, Yangsan 50612, South Korea
- Medical Education, Pusan National University School of Medicine, Yangsan 50760, South Korea
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2
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Chao J, Coleman RA, Keating DJ, Martin AM. Gut Microbiome Regulation of Gut Hormone Secretion. Endocrinology 2025; 166:bqaf004. [PMID: 40037297 PMCID: PMC11879239 DOI: 10.1210/endocr/bqaf004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2024] [Indexed: 03/06/2025]
Abstract
The gut microbiome, comprising bacteria, viruses, fungi, and bacteriophages, is one of the largest microbial ecosystems in the human body and plays a crucial role in various physiological processes. This review explores the interaction between the gut microbiome and enteroendocrine cells (EECs), specialized hormone-secreting cells within the intestinal epithelium. EECs, which constitute less than 1% of intestinal epithelial cells, are key regulators of gut-brain communication, energy metabolism, gut motility, and satiety. Recent evidence shows that gut microbiota directly influence EEC function, maturation, and hormone secretion. For instance, commensal bacteria regulate the production of hormones like glucagon-like peptide 1 and peptide YY by modulating gene expression and vesicle cycling in EE cells. Additionally, metabolites such as short-chain fatty acids, derived from microbial fermentation, play a central role in regulating EEC signaling pathways that affect metabolism, gut motility, and immune responses. Furthermore, the interplay between gut microbiota, EECs, and metabolic diseases, such as obesity and diabetes, is examined, emphasizing the microbiome's dual role in promoting health and contributing to disease states. This intricate relationship between the gut microbiome and EECs offers new insights into potential therapeutic strategies for metabolic and gut disorders.
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Affiliation(s)
- Jessica Chao
- Gut Hormones in Health and Disease Lab, Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Adelaide 5042, Australia
| | - Rosemary A Coleman
- Gut Hormones in Health and Disease Lab, Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Adelaide 5042, Australia
| | - Damien J Keating
- Gut Sensory Systems Group, Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Adelaide 5042, Australia
| | - Alyce M Martin
- Gut Hormones in Health and Disease Lab, Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Adelaide 5042, Australia
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Lang H, Xiang J, Chen X, Tong D, Wang L, Mou A, Liu D, Gao P, Lu Z, Zhu Z. Roux-en-Y gastric bypass alleviates kidney inflammation and improves kidney function in db/db mice by activating TLCA/TGR5 pathway. Am J Physiol Endocrinol Metab 2025; 328:E148-E160. [PMID: 39681344 DOI: 10.1152/ajpendo.00248.2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Revised: 11/07/2024] [Accepted: 12/02/2024] [Indexed: 12/18/2024]
Abstract
Diabetic kidney disease (DKD) is a severe diabetic microvascular complication featured by chronic low-grade inflammation. Roux-en-Y gastric bypass (RYGB) surgery has gained importance as a safe and effective surgery to treat DKD. Bile acids significantly change after RYGB, which brings a series of metabolic benefits, but the relationship with the improvement of DKD is unclear. Therefore, this study performed RYGB surgery on db/db mice to observe the beneficial effects of the surgery on the kidneys and performed bile acid-targeted metabolomics analysis to explore bile acid changes. We found that RYGB significantly reduced albuminuria in db/db mice, improved renal function, reversed renal structural lesions, and attenuated podocyte injury and inflammation. Notably, bile acid metabolomic analysis revealed taurolithocholic acid (TLCA) as the most significantly altered bile acid after RYGB. Furthermore, in vitro and in vivo validation experiments revealed that TLCA supplementation improved renal function and reduced renal inflammatory damage in db/db mice. In addition, TLCA inhibited high glucose-induced inflammatory damage in MPC-5 cells, and its mechanism of action may be related to activating Takeda G protein-coupled receptor 5 (TGR5), inhibiting NF-κB phosphorylation, and thus inhibiting inflammatory response. In conclusion, RYGB may play a protective role in the kidneys of diabetic mice by activating the TLCA/TGR5 pathway.NEW & NOTEWORTHY This study determined that the renal protective effect of Roux-en-Y gastric bypass (RYGB) in db/db mice was associated with elevated serum TLCA. Notably, TLCA supplementation improved renal function and alleviated podocyte inflammatory injury in db/db mice, which was associated with the TGR5/NF-κB pathway.
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Affiliation(s)
- Hongmei Lang
- Department of General Medicine, Chengdu Second People's Hospital, Chengdu, People's Republic of China
| | - Jie Xiang
- Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, Army Medical University, Chongqing Institute of Hypertension, Chongqing, People's Republic of China
| | - Xiaorong Chen
- Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, Army Medical University, Chongqing Institute of Hypertension, Chongqing, People's Republic of China
| | - Dan Tong
- Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, Army Medical University, Chongqing Institute of Hypertension, Chongqing, People's Republic of China
| | - Lijuan Wang
- Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, Army Medical University, Chongqing Institute of Hypertension, Chongqing, People's Republic of China
| | - Aidi Mou
- Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, Army Medical University, Chongqing Institute of Hypertension, Chongqing, People's Republic of China
| | - Daoyan Liu
- Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, Army Medical University, Chongqing Institute of Hypertension, Chongqing, People's Republic of China
| | - Peng Gao
- Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, Army Medical University, Chongqing Institute of Hypertension, Chongqing, People's Republic of China
| | - Zongshi Lu
- Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, Army Medical University, Chongqing Institute of Hypertension, Chongqing, People's Republic of China
| | - Zhiming Zhu
- Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, Army Medical University, Chongqing Institute of Hypertension, Chongqing, People's Republic of China
- Chongqing Institute for Brain and Intelligence, Chongqing, People's Republic of China
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Barbut D, Kinney WA, Chen HH, Stewart AFR, Hecksher-Sørensen J, Zhang C, Fleming A, Zemel M, Zasloff M. A novel, centrally acting mammalian aminosterol, ENT-03, induces weight loss in obese and lean rodents. Diabetes Obes Metab 2024; 26:5701-5712. [PMID: 39307948 DOI: 10.1111/dom.15940] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2024] [Revised: 08/10/2024] [Accepted: 08/22/2024] [Indexed: 11/05/2024]
Abstract
ENT-03, a spermine bile acid we recently discovered in the brain of newborn mice acts centrally to regulate energy and metabolism. Obese, diabetic (ob/ob) mice treated with five doses of ENT-03 over 2 weeks, demonstrated a rapid decrease in blood glucose levels into the range seen in non-obese animals, prior to any significant weight loss. Weight fell substantially thereafter as food intake decreased, and serum biochemical parameters normalized compared with both vehicle and pair-fed controls. To determine whether ENT-03 could be acting centrally, we injected a single dose of ENT-03 intracerebroventricularly to Sprague-Dawley rats. Weight fell significantly and remained below vehicle injected controls for an extended period. By autoradiography, ENT-03 localized to the arcuate nucleus of the hypothalamus, the choroid plexus and cerebrospinal fluid. Significant cFos activation occurred in multiple anatomical regions within the hypothalamus and brainstem involved in appetite suppression, food-entrained circadian rhythmicity, autonomic function, and growth. These data support a role for ENT-03 in the treatment of type 2 diabetes and obesity. Phase 1 studies in subjects with obesity and diabetes are currently in progress.
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Affiliation(s)
- Denise Barbut
- Enterin, Inc., Philadelphia, Pennsylvania, USA
- Enterin Research Institute, Philadelphia, Pennsylvania, USA
| | - William A Kinney
- Enterin, Inc., Philadelphia, Pennsylvania, USA
- Enterin Research Institute, Philadelphia, Pennsylvania, USA
| | | | | | | | | | | | | | - Michael Zasloff
- Enterin, Inc., Philadelphia, Pennsylvania, USA
- Enterin Research Institute, Philadelphia, Pennsylvania, USA
- MedStar Georgetown Transplant Institute, Washington, District of Columbia, USA
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Li S, Shi C, Wu H, Yan H, Xia M, Jiao H, He Y, Zhong M, Lou W, Gao X, Bian H, Chang X. Longitudinal changes of serum metabolomic profile after laparoscopic sleeve gastrectomy in obesity. Endocr Connect 2024; 13:e240292. [PMID: 39302038 PMCID: PMC11562687 DOI: 10.1530/ec-24-0292] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Accepted: 09/20/2024] [Indexed: 09/22/2024]
Abstract
Background Bariatric surgery induces significant weight loss, increases insulin sensitivity, and improves dyslipidemia. As one of the most widely performed bariatric surgeries, laparoscopic sleeve gastrectomy (LSG) is thought to improve the metabolic profile along with weight loss. The objective of this study was to evaluate longitudinal changes in the serum metabolite levels after LSG and elucidate the underlying mechanisms of metabolic improvement. Methods Clinical metabolic parameters and serum samples were collected preoperatively and at 1, 3, and 6 months postoperatively from nine patients with obesity undergoing LSG. Serum metabolites were measured using a non-targeted metabolic liquid chromatography-mass spectrometry method. Results During the 1, 3, and 6 months postoperative follow-up, the body mass index, HOMA-IR, and liver fat content showed a gradual descending trend. A total of 328 serum metabolites were detected, and 38 were differentially expressed. The up-regulated metabolites were mainly enriched in ketone body metabolism, alpha-linolenic acid and linoleic acid metabolism, pantothenate and CoA biosynthesis, glycerolipid metabolism, and fructose and mannose degradation, while the down-regulated metabolites were closely related to caffeine metabolism, oxidation of branched-chain fatty acids, glutamate metabolism, and homocysteine degradation. Notably, nine metabolites (oxoglutarate, 2-ketobutyric acid, succinic acid semialdehyde, phthalic acid, pantetheine, eicosapentaenoate, 3-hydroxybutanoate, oxamic acid, and dihydroxyfumarate) showed persistent differential expression at 1, 3, and 6 months follow-up. Some were found to be significantly associated with weight loss, insulin resistance improvement, and liver fat content reduction. Conclusions This finding may provide a new perspective for revealing novel biomarkers and mechanisms of metabolic improvement in obesity and related comorbidities.
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Affiliation(s)
- Shuqi Li
- Department of Endocrinology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Chenye Shi
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Haifu Wu
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Hongmei Yan
- Department of Endocrinology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Mingfeng Xia
- Department of Endocrinology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Heng Jiao
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yang He
- Department of Endocrinology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Ming Zhong
- Department of Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Wenhui Lou
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xin Gao
- Department of Endocrinology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Hua Bian
- Department of Endocrinology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xinxia Chang
- Department of Endocrinology, Zhongshan Hospital, Fudan University, Shanghai, China
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Li T, Chiang JYL. Bile Acid Signaling in Metabolic and Inflammatory Diseases and Drug Development. Pharmacol Rev 2024; 76:1221-1253. [PMID: 38977324 PMCID: PMC11549937 DOI: 10.1124/pharmrev.124.000978] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Revised: 06/26/2024] [Accepted: 06/28/2024] [Indexed: 07/10/2024] Open
Abstract
Bile acids are the end products of cholesterol catabolism. Hepatic bile acid synthesis accounts for a major fraction of daily cholesterol turnover in humans. Biliary secretion of bile acids generates bile flow and facilitates biliary secretion of lipids, endogenous metabolites, and xenobiotics. In intestine, bile acids facilitate the digestion and absorption of dietary lipids and fat-soluble vitamins. Through activation of nuclear receptors and G protein-coupled receptors and interaction with gut microbiome, bile acids critically regulate host metabolism and innate and adaptive immunity and are involved in the pathogenesis of cholestasis, metabolic dysfunction-associated steatotic liver disease, alcohol-associated liver disease, type-2 diabetes, and inflammatory bowel diseases. Bile acids and their derivatives have been developed as potential therapeutic agents for treating chronic metabolic and inflammatory liver diseases and gastrointestinal disorders. SIGNIFICANCE STATEMENT: Bile acids facilitate biliary cholesterol solubilization and dietary lipid absorption, regulate host metabolism and immunity, and modulate gut microbiome. Targeting bile acid metabolism and signaling holds promise for treating metabolic and inflammatory diseases.
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Affiliation(s)
- Tiangang Li
- Department of Biochemistry and Physiology, Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma (T.L.); and Department of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, Ohio (J.Y.L.C.)
| | - John Y L Chiang
- Department of Biochemistry and Physiology, Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma (T.L.); and Department of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, Ohio (J.Y.L.C.)
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Han L, Chen X, Wan D, Xie M, Ouyang S. One anastomosis gastric bypass ameliorates diabetic nephropathy via regulating the GLP-1-mediated Sirt1/AMPK/PGC1α pathway. Clin Exp Nephrol 2024; 28:1051-1061. [PMID: 38782822 DOI: 10.1007/s10157-024-02516-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2024] [Accepted: 05/13/2024] [Indexed: 05/25/2024]
Abstract
BACKGROUND Diabetic nephropathy (DN), a complication of diabetes, is the most leading cause of end-stage renal disease. Bariatric surgery functions on the remission of diabetes and diabetes-related complications. One anastomosis gastric bypass (OAGB), one of popular bariatric surgery, can improve diabetes and its complications by regulating the glucagon-like peptide-1 (GLP-1) level. Meanwhile, GLP-1 can alleviate renal damage in high-fat-diet-induced obese rats. However, the effect of OAGB on renal injury remains uncertain in DN. METHODS A diabetes model was elicited in rats via HFD feeding and STZ injection. The role and mechanism of OAGB were addressed in DN rats by the body and kidney weight and blood glucose supervision, oral glucose tolerance test (OGTT), enzyme-linked immunosorbent assay (ELISA), biochemistry detection, histopathological analysis, and western blot assays. RESULTS OAGB surgery reversed the increase in body weight and glucose tolerance indicators in diabetes rats. Also, OAGB operation neutralized the DN-induced average kidney weight, kidney weight/body weight, and renal injury indexes accompanied with reduced glomerular hypertrophy, alleviated mesangial dilation and decreased tubular and periglomerular collagen deposition. In addition, OAGB introduction reduced the DN-induced renal triglyceride and renal cholesterol with the regulation of fatty acids-related proteins expression. Mechanically, OAGB administration rescued the DN-induced expression of Sirt1/AMPK/PGC1α pathway mediated by GLP-1. Pharmacological block of GLP-1 receptor inverted the effect of OAGB operation on body weight, glucose tolerance, renal tissue damage, and fibrosis and lipids accumulation in DN rats. CONCLUSION OAGB improved renal damage and fibrosis and lipids accumulation in DN rats by GLP-1-mediated Sirt1/AMPK/PGC1α pathway.
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Affiliation(s)
- Lang Han
- Department of General Surgery, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, No. 149, Dalian Road, Huichuan, Zunyi, 563000, Guizhou, China
| | - Xiaojiao Chen
- Department of General Surgery, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, No. 149, Dalian Road, Huichuan, Zunyi, 563000, Guizhou, China
| | - Dianwei Wan
- Department of General Surgery, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, No. 149, Dalian Road, Huichuan, Zunyi, 563000, Guizhou, China
| | - Min Xie
- Department of General Surgery, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, No. 149, Dalian Road, Huichuan, Zunyi, 563000, Guizhou, China
| | - Shurui Ouyang
- Department of General Surgery, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, No. 149, Dalian Road, Huichuan, Zunyi, 563000, Guizhou, China.
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Wei M, Tu W, Huang G. Regulating bile acids signaling for NAFLD: molecular insights and novel therapeutic interventions. Front Microbiol 2024; 15:1341938. [PMID: 38887706 PMCID: PMC11180741 DOI: 10.3389/fmicb.2024.1341938] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2023] [Accepted: 05/14/2024] [Indexed: 06/20/2024] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) emerges as the most predominant cause of liver disease, tightly linked to metabolic dysfunction. Bile acids (BAs), initially synthesized from cholesterol in the liver, undergo further metabolism by gut bacteria. Increasingly acknowledged as critical modulators of metabolic processes, BAs have been implicated as important signaling molecules. In this review, we will focus on the mechanism of BAs signaling involved in glucose homeostasis, lipid metabolism, energy expenditure, and immune regulation and summarize their roles in the pathogenesis of NAFLD. Furthermore, gut microbiota dysbiosis plays a key role in the development of NAFLD, and the interactions between BAs and intestinal microbiota is elucidated. In addition, we also discuss potential therapeutic strategies for NAFLD, including drugs targeting BA receptors, modulation of intestinal microbiota, and metabolic surgery.
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Affiliation(s)
- Meilin Wei
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Wei Tu
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Genhua Huang
- Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Nanchang University, Nanchang, China
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Li Q, Byun J, Choi J, Park J, Lee J, Oh YK. Nanomodulator-Mediated Restructuring of Adipose Tissue Immune Microenvironments for Antiobesity Treatment. ACS NANO 2024; 18:9311-9330. [PMID: 38498418 DOI: 10.1021/acsnano.3c06001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/20/2024]
Abstract
In obesity, the interactions between proinflammatory macrophages and adipocytes in white adipose tissues are known to play a crucial role in disease progression by providing inflammatory microenvironments. Here, we report that the functional nanoparticle-mediated modulation of crosstalk between adipocytes and macrophages can remodel adipocyte immune microenvironments. As a functional nanomodulator, we designed antivascular cell adhesion molecule (VCAM)-1 antibody-conjugated and amlexanox-loaded polydopamine nanoparticles (VAPN). Amlexanox was used as a model drug to increase energy expenditure. Compared to nanoparticles lacking antibody modification or amlexanox, VAPN showed significantly greater binding to VCAM-1-expressing adipocytes and lowered the interaction of adipocytes with macrophages. In high fat diet-fed mice, repeated subcutaneous administration of VAPN increased the populations of beige adipocytes and ameliorated inflammation in white adipose tissues. Moreover, the localized application of VAPN in vivo exerted a systemic metabolic effect and reduced metabolic disorders, including insulin tolerance and liver steatosis. These findings suggested that VAPN had potential to modulate the immune microenvironments of adipose tissues for the immunologic treatment of obesity. Although we used amlexanox as a model drug and anti-VCAM-1 antibody in VAPN, the concept of immune nanomodulators can be widely applied to the immunological treatment of obesity.
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Affiliation(s)
- Qiaoyun Li
- College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Republic of Korea
| | - Junho Byun
- College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Republic of Korea
| | - Jaehyun Choi
- College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Republic of Korea
| | - Jinwon Park
- College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Republic of Korea
| | - Jaiwoo Lee
- College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Republic of Korea
| | - Yu-Kyoung Oh
- College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Republic of Korea
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Akbuğa-Schön T, Suzuki TA, Jakob D, Vu DL, Waters JL, Ley RE. The keystone gut species Christensenella minuta boosts gut microbial biomass and voluntary physical activity in mice. mBio 2024; 15:e0283623. [PMID: 38132571 PMCID: PMC10865807 DOI: 10.1128/mbio.02836-23] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2023] [Accepted: 10/26/2023] [Indexed: 12/23/2023] Open
Abstract
The gut bacteria of the family Christensenellaceae are consistently associated with metabolic health, but their role in promoting host health is not fully understood. Here, we explored the effect of Christensenella minuta amendment on voluntary physical activity and the gut microbiome. We inoculated male and female germ-free mice with an obese human donor microbiota together with live or heat-killed C. minuta for 28 days and measured physical activity in respirometry cages. Compared to heat-killed, the live-C. minuta treatment resulted in reduced feed efficiency and higher levels of physical activity, with significantly greater distance traveled for males and higher levels of small movements and resting metabolic rate in females. Sex-specific effects of C. minuta treatment may be in part attributable to different housing conditions for males and females. Amendment with live C. minuta boosted gut microbial biomass in both sexes, immobilizing dietary carbon in the microbiome, and mice with high levels of C. minuta lose more energy in stool. Live C. minuta also reduced within and between-host gut microbial diversity. Overall, our results showed that C. minuta acts as a keystone species: despite low relative abundance, it has a large impact on its ecosystem, from the microbiome to host energy homeostasis.IMPORTANCEThe composition of the human gut microbiome is associated with human health. Within the human gut microbiome, the relative abundance of the bacterial family Christensenellaceae has been shown to correlate with metabolic health and a lean body type. The mechanisms underpinning this effect remain unclear. Here, we show that live C. minuta influences host physical activity and metabolic energy expenditure, accompanied by changes in murine metabolism and the gut microbial community in a sex-dependent manner in comparison to heat-killed C. minuta. Importantly, live C. minuta boosts the biomass of the microbiome in the gut, and a higher level of C. minuta is associated with greater loss of energy in stool. These observations indicate that modulation of activity levels and changes to the microbiome are ways in which the Christensenellaceae can influence host energy homeostasis and health.
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Affiliation(s)
- Tanja Akbuğa-Schön
- Department of Microbiome Science, Max Planck Institute for Biology Tübingen, Tübingen, Germany
| | - Taichi A. Suzuki
- Department of Microbiome Science, Max Planck Institute for Biology Tübingen, Tübingen, Germany
| | - Dennis Jakob
- Department of Microbiome Science, Max Planck Institute for Biology Tübingen, Tübingen, Germany
- Mass Spectrometry Facility, Max Planck Institute for Biology Tübingen, Tübingen, Germany
| | - Dai Long Vu
- Mass Spectrometry Facility, Max Planck Institute for Biology Tübingen, Tübingen, Germany
| | - Jillian L. Waters
- Department of Microbiome Science, Max Planck Institute for Biology Tübingen, Tübingen, Germany
| | - Ruth E. Ley
- Department of Microbiome Science, Max Planck Institute for Biology Tübingen, Tübingen, Germany
- Cluster of Excellence EXC 2124 Controlling Microbes to Fight Infections, University of Tübingen, Tübingen, Germany
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11
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Evans LL, Lee WG, Karimzada M, Patel VH, Aribindi VK, Kwiat D, Graham JL, Cummings DE, Havel PJ, Harrison MR. Evaluation of a Magnetic Compression Anastomosis for Jejunoileal Partial Diversion in Rhesus Macaques. Obes Surg 2024; 34:515-523. [PMID: 38135738 PMCID: PMC10810932 DOI: 10.1007/s11695-023-07012-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Revised: 12/15/2023] [Accepted: 12/15/2023] [Indexed: 12/24/2023]
Abstract
PURPOSE Metabolic surgery remains underutilized for treating type 2 diabetes, as less invasive alternative interventions with improved risk profiles are needed. We conducted a pilot study to evaluate the feasibility of a novel magnetic compression device to create a patent limited caliber side-to-side jejunoileal partial diversion in a nonhuman primate model. MATERIALS AND METHODS Using an established nonhuman primate model of diet-induced insulin resistance, a magnetic compression device was used to create a side-to-side jejunoileal anastomosis. Primary outcomes evaluated feasibility (e.g., device mating and anastomosis patency) and safety (e.g., device-related complications). Secondary outcomes evaluated the device's ability to produce metabolic changes associated with jejunoileal partial diversion (e.g., homeostatic model assessment of insulin resistance [HOMA-IR] and body weight). RESULTS Device mating, spontaneous detachment, and excretion occurred in all animals (n = 5). There were no device-related adverse events. Upon completion of the study, ex vivo anastomoses were widely patent with healthy mucosa and no evidence of stricture. At 6 weeks post-device placement, HOMA-IR improved to below baseline values (p < 0.05). Total weight also decreased in a linear fashion (R2 = 0.97) with total weight loss at 6 weeks post-device placement of 14.4% (p < 0.05). CONCLUSION The use of this novel magnetic compression device to create a limited caliber side-to-side jejunoileal anastomosis is safe and likely feasible in a nonhuman primate model. The observed glucoregulatory and metabolic effects of a partial jejunoileal bypass with this device warrant further investigation to validate the long-term glucometabolic impact of this approach.
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Affiliation(s)
- Lauren L Evans
- Department of Surgery, University of California San Francisco, San Francisco, USA
| | - William G Lee
- Department of Surgery, University of California San Francisco, San Francisco, USA
| | - Mohammad Karimzada
- Department of Surgery, University of California San Francisco, San Francisco, USA
| | - Veeshal H Patel
- Department of Surgery, University of California San Francisco, San Francisco, USA
| | - Vamsi K Aribindi
- Department of Surgery, University of California San Francisco, San Francisco, USA
| | - Dillon Kwiat
- Department of Surgery, University of California San Francisco, San Francisco, USA
| | - James L Graham
- Department of Molecular Biosciences, School of Veterinary Medicine and Department of Nutrition, University of California Davis, Davis, USA
| | - David E Cummings
- Division of Metabolism, Endocrinology and Nutrition, University of Washington and VA Puget Sound Health Care System, Seattle, USA
| | - Peter J Havel
- Department of Molecular Biosciences, School of Veterinary Medicine and Department of Nutrition, University of California Davis, Davis, USA
| | - Michael R Harrison
- Department of Surgery, University of California San Francisco, San Francisco, USA.
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12
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Igwe JK, Surapaneni PK, Cruz E, Cole C, Njoku K, Kim J, Alaribe U, Weze K, Mohammed B. Bariatric Surgery and Inflammatory Bowel Disease: National Trends and Outcomes Associated with Procedural Sleeve Gastrectomy vs Historical Bariatric Surgery Among US Hospitalized Patients 2009-2020. Obes Surg 2023; 33:3472-3486. [PMID: 37804470 PMCID: PMC10603008 DOI: 10.1007/s11695-023-06833-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Revised: 09/04/2023] [Accepted: 09/15/2023] [Indexed: 10/09/2023]
Abstract
PURPOSE The association between bariatric surgery and IBD-related inpatient outcomes is not well characterized. We report, analyze, and compare inpatient trends and outcomes among encounters with a history of bariatric surgery (Hx-MBS) compared to those receiving bariatric surgery during index admission (PR-MBS) admitted from 2009 to 2020. METHODS Retrospective cohort design: the 2009-2020 National Inpatient Sample (NIS) databases were used to identify hospital encounters with patients aged ≥ 18 years with a history of MBS (Hx-MBS) or with procedure coding indicating MBS procedure (PR-MBS) according to International Classification of Diseases, Ninth (ICD-9-CM/ ICD-9-PCS) or Tenth Revision (ICD-10-CM/ICD-10-PCS) Clinical Modification/Procedure Coding System during index admission (ICD-9-CM: V4586; ICD-10-CM: Z9884; ICD-9-PR: 4382, 4389; ICD-10-PR: 0DB64Z3, 0DB63ZZ). Pearson χ2 analysis, analysis of variance, multivariable regression analyses, and propensity matching on independent variables were conducted to analyze significant associations between variables and for primary outcome inflammatory bowel disease-related admission, and secondary outcomes: diagnosis of nonalcoholic steatohepatitis, nonalcoholic fatty liver disease, or chronic mesenteric ischemia during admission. RESULTS We identified 3,365,784 (76.20%) Hx-MBS hospitalizations and 1,050,900 hospitalizations with PR-MBS (23.80%). Propensity score matching analysis demonstrated significantly higher odds of inflammatory bowel disease, and chronic mesenteric ischemia for Hx-MBS compared to PR-MBS, and significantly lower odds of nonalcoholic steatohepatitis and nonalcoholic fatty liver disease for Hx-MBS compared to PR-MBS. CONCLUSION In our study, Hx-MBS was associated with significantly increased odds of inflammatory bowel disease and other GI pathologies compared to matched controls. The mechanism by which this occurs is unclear. Additional studies are needed to examine these findings.
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Affiliation(s)
- Joseph-Kevin Igwe
- School of Medicine, Department of Medicine, Stanford University, 291 Campus Drive, Stanford, CA, 94305, USA.
- Department of Medicine, Morehouse School of Medicine, 720 Westview Dr. SW, Atlanta, GA, 30313, USA.
- American Heart Association Strategically Focused Research Network on the Science of Diversity in Clinical Trials Research Fellowship, 5001 S Miami Blvd #300, Durham, NC, 27703, USA.
| | | | - Erin Cruz
- School of Medicine, Department of Medicine, Stanford University, 291 Campus Drive, Stanford, CA, 94305, USA
| | - Cedric Cole
- Department of Medicine, Morehouse School of Medicine, 720 Westview Dr. SW, Atlanta, GA, 30313, USA
| | - Kingsley Njoku
- Department of Medicine, Emory University School of Medicine, Atlanta, USA
| | - Jisoo Kim
- Department of Surgery, Texas Tech University Health Sciences Center at El Paso, El Paso, USA
| | - Ugo Alaribe
- School of Medicine, Caribbean Medical University, Willemstad, USA
| | - Kelechi Weze
- Department of Medicine, Morehouse School of Medicine, 720 Westview Dr. SW, Atlanta, GA, 30313, USA
| | - Bilal Mohammed
- Department of Medicine, Ascension Saint Vincent, Indianapolis, USA
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13
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Zanella D, Smith NK, Hardaway JA, Buchanan AM, Mullins CH, Galli A, Carter AM. Bile acids modulate reinstatement of cocaine conditioned place preference and accumbal dopamine dynamics without compromising appetitive learning. Sci Rep 2023; 13:13359. [PMID: 37591972 PMCID: PMC10435481 DOI: 10.1038/s41598-023-40456-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Accepted: 08/10/2023] [Indexed: 08/19/2023] Open
Abstract
Psychostimulants target the dopamine transporter (DAT) to elicit their psychomotor actions. Bile acids (BAs) can also bind to DAT and reduce behavioral responses to cocaine, suggesting a potential therapeutic application of BAs in psychostimulant use disorder. Here, we investigate the potential of BAs to decrease drug-primed reinstatement when administered during an abstinence phase. To do this, after successful development of cocaine-associated contextual place preference (cocaine CPP), cocaine administration was terminated, and animals treated with vehicle or obeticholic acid (OCA). When preference for the cocaine-associated context was extinguished, mice were challenged with a single priming dose of cocaine, and reinstatement of cocaine-associated contextual preference was measured. Animals treated with OCA demonstrate a significantly lower reinstatement for cocaine CPP. OCA also impairs the ability of cocaine to reduce the clearance rate of electrically stimulated dopamine release and diminishes the area under the curve (AUC) observed with amperometry. Furthermore, the AUC of the amperometric signal positively correlates with the reinstatement index. Using operant feeding devices, we demonstrate that OCA has no effect on contextual learning or motivation for natural rewards. These data highlight OCA as a potential therapeutic for cocaine use disorder.
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Affiliation(s)
- Daniele Zanella
- Department of Surgery, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, USA
| | - Nicholas K Smith
- Department of Biology, University of Pennsylvania, Philadelphia, USA
| | - J Andrew Hardaway
- Department of Psychiatry and Behavioral Neurobiology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, USA
| | - Anna Marie Buchanan
- Department of Surgery, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, USA
| | - Clarence H Mullins
- Department of Surgery, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, USA
| | - Aurelio Galli
- Department of Surgery, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, USA
- Center for Inter-Systemic Networks and Enteric Medical Advances (UAB CINEMA), Birmingham, USA
| | - Angela M Carter
- Department of Surgery, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, USA.
- Center for Inter-Systemic Networks and Enteric Medical Advances (UAB CINEMA), Birmingham, USA.
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14
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Masse KE, Lu VB. Short-chain fatty acids, secondary bile acids and indoles: gut microbial metabolites with effects on enteroendocrine cell function and their potential as therapies for metabolic disease. Front Endocrinol (Lausanne) 2023; 14:1169624. [PMID: 37560311 PMCID: PMC10407565 DOI: 10.3389/fendo.2023.1169624] [Citation(s) in RCA: 26] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2023] [Accepted: 07/05/2023] [Indexed: 08/11/2023] Open
Abstract
The gastrointestinal tract hosts the largest ecosystem of microorganisms in the body. The metabolism of ingested nutrients by gut bacteria produces novel chemical mediators that can influence chemosensory cells lining the gastrointestinal tract. Specifically, hormone-releasing enteroendocrine cells which express a host of receptors activated by these bacterial metabolites. This review will focus on the activation mechanisms of glucagon-like peptide-1 releasing enteroendocrine cells by the three main bacterial metabolites produced in the gut: short-chain fatty acids, secondary bile acids and indoles. Given the importance of enteroendocrine cells in regulating glucose homeostasis and food intake, we will also discuss therapies based on these bacterial metabolites used in the treatment of metabolic diseases such as diabetes and obesity. Elucidating the mechanisms gut bacteria can influence cellular function in the host will advance our understanding of this fundamental symbiotic relationship and unlock the potential of harnessing these pathways to improve human health.
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Affiliation(s)
| | - Van B. Lu
- Department of Physiology and Pharmacology, University of Western Ontario, London, ON, Canada
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15
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Zhang Y, Liu L, Wei C, Wang X, Li R, Xu X, Zhang Y, Geng G, Dang K, Ming Z, Tao X, Xu H, Yan X, Zhang J, Hu J, Li Y. Vitamin K2 supplementation improves impaired glycemic homeostasis and insulin sensitivity for type 2 diabetes through gut microbiome and fecal metabolites. BMC Med 2023; 21:174. [PMID: 37147641 PMCID: PMC10163743 DOI: 10.1186/s12916-023-02880-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2023] [Accepted: 04/25/2023] [Indexed: 05/07/2023] Open
Abstract
BACKGROUND There is insufficient evidence for the ability of vitamin K2 to improve type 2 diabetes mellitus symptoms by regulating gut microbial composition. Herein, we aimed to demonstrate the key role of the gut microbiota in the improvement of impaired glycemic homeostasis and insulin sensitivity by vitamin K2 intervention. METHODS We first performed a 6-month RCT on 60 T2DM participants with or without MK-7 (a natural form of vitamin K2) intervention. In addition, we conducted a transplantation of the MK-7-regulated microbiota in diet-induced obesity mice for 4 weeks. 16S rRNA sequencing, fecal metabolomics, and transcriptomics in both study phases were used to clarify the potential mechanism. RESULTS After MK-7 intervention, we observed notable 13.4%, 28.3%, and 7.4% reductions in fasting serum glucose (P = 0.048), insulin (P = 0.005), and HbA1c levels (P = 0.019) in type 2 diabetes participants and significant glucose tolerance improvement in diet-induced obesity mice (P = 0.005). Moreover, increased concentrations of secondary bile acids (lithocholic and taurodeoxycholic acid) and short-chain fatty acids (acetic acid, butyric acid, and valeric acid) were found in human and mouse feces accompanied by an increased abundance of the genera that are responsible for the biosynthesis of these metabolites. Finally, we found that 4 weeks of fecal microbiota transplantation significantly improved glucose tolerance in diet-induced obesity mice by activating colon bile acid receptors, improving host immune-inflammatory responses, and increasing circulating GLP-1 concentrations. CONCLUSIONS Our gut-derived findings provide evidence for a regulatory role of vitamin K2 on glycemic homeostasis, which may further facilitate the clinical implementation of vitamin K2 intervention for diabetes management. TRIAL REGISTRATION The study was registered at https://www.chictr.org.cn (ChiCTR1800019663).
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Affiliation(s)
- Yuntao Zhang
- Department of Nutrition and Food Hygiene, the National Key Discipline, School of Public Health, Harbin Medical University, Harbin, China
| | - Lin Liu
- Department of Nutrition and Food Hygiene, the National Key Discipline, School of Public Health, Harbin Medical University, Harbin, China
| | - Chunbo Wei
- Department of Nutrition and Food Hygiene, the National Key Discipline, School of Public Health, Harbin Medical University, Harbin, China
| | - Xuanyang Wang
- Department of Nutrition and Food Hygiene, the National Key Discipline, School of Public Health, Harbin Medical University, Harbin, China
| | - Ran Li
- Department of Nutrition, the Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Xiaoqing Xu
- Department of Nutrition and Food Hygiene, the National Key Discipline, School of Public Health, Harbin Medical University, Harbin, China
| | - Yingfeng Zhang
- Department of Nutrition and Food Hygiene, the National Key Discipline, School of Public Health, Harbin Medical University, Harbin, China
| | - Guannan Geng
- Department of Endocrinology, the First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Keke Dang
- Department of Nutrition and Food Hygiene, the National Key Discipline, School of Public Health, Harbin Medical University, Harbin, China
| | - Zhu Ming
- Department of Nutrition and Food Hygiene, the National Key Discipline, School of Public Health, Harbin Medical University, Harbin, China
| | - Xinmiao Tao
- Department of Nutrition and Food Hygiene, the National Key Discipline, School of Public Health, Harbin Medical University, Harbin, China
| | - Huan Xu
- Department of Nutrition and Food Hygiene, the National Key Discipline, School of Public Health, Harbin Medical University, Harbin, China
| | - Xuemin Yan
- Department of Nutrition and Food Hygiene, the National Key Discipline, School of Public Health, Harbin Medical University, Harbin, China
| | - Jia Zhang
- Department of Nutrition and Food Hygiene, the National Key Discipline, School of Public Health, Harbin Medical University, Harbin, China
| | - Jinxia Hu
- Department of Nutrition and Food Hygiene, the National Key Discipline, School of Public Health, Harbin Medical University, Harbin, China
| | - Ying Li
- Department of Nutrition and Food Hygiene, the National Key Discipline, School of Public Health, Harbin Medical University, Harbin, China.
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16
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Abstract
PURPOSE OF REVIEW This review aims to provide a concise update on recent advances in understanding of the bile acid metabolism and signaling in health and diseases. RECENT FINDINGS CYP2C70 has been identified as the murine cytochrome p450 enzyme that mediates the synthesis of muricholic acids to account for the major different bile acid composition between human and mice. Several studies have linked nutrient sensing bile acid signaling to the regulation of hepatic autophagy-lysosome activity, an integral pathway of the cellular adaptive response to starvation. Distinct bile acid-mediated signaling mechanisms have been shown to contribute to the complex metabolic changes post bariatric surgery, suggesting that pharmacological manipulation of the enterohepatic bile acid signaling could be a potential nonsurgical alternative to weight loss surgery. SUMMARY Basic and clinical studies have continued to discover novel roles of the enterohepatic bile acid signaling in regulation of key metabolic pathways. Such knowledge forms the molecular basis needed for developing safe and effective bile acid-based therapeutics for treating metabolic and inflammatory diseases.
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Affiliation(s)
- Tiangang Li
- Department of Physiology, Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
| | - John Y L Chiang
- Department of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, Ohio, USA
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17
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Louca P, Meijnikman AS, Nogal A, Asnicar F, Attaye I, Vijay A, Kouraki A, Visconti A, Wong K, Berry SE, Leeming ER, Mompeo O, Tettamanzi F, Baleanu AF, Falchi M, Hadjigeorgiou G, Wolf J, Acherman YIZ, Van de Laar AW, Gerdes VEA, Michelotti GA, Franks PW, Segata N, Mangino M, Spector TD, Bulsiewicz WJ, Nieuwdorp M, Valdes AM, Menni C. The secondary bile acid isoursodeoxycholate correlates with post-prandial lipemia, inflammation, and appetite and changes post-bariatric surgery. Cell Rep Med 2023; 4:100993. [PMID: 37023745 PMCID: PMC10140478 DOI: 10.1016/j.xcrm.2023.100993] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2022] [Revised: 10/12/2022] [Accepted: 03/14/2023] [Indexed: 04/08/2023]
Abstract
Primary and secondary bile acids (BAs) influence metabolism and inflammation, and the gut microbiome modulates levels of BAs. We systematically explore the host genetic, gut microbial, and habitual dietary contribution to a panel of 19 serum and 15 stool BAs in two population-based cohorts (TwinsUK, n = 2,382; ZOE PREDICT-1, n = 327) and assess changes post-bariatric surgery and after nutritional interventions. We report that BAs have a moderately heritable genetic component, and the gut microbiome accurately predicts their levels in serum and stool. The secondary BA isoursodeoxycholate (isoUDCA) can be explained mostly by gut microbes (area under the receiver operating characteristic curve [AUC] = ∼80%) and associates with post-prandial lipemia and inflammation (GlycA). Furthermore, circulating isoUDCA decreases significantly 1 year after bariatric surgery (β = -0.72, p = 1 × 10-5) and in response to fiber supplementation (β = -0.37, p < 0.03) but not omega-3 supplementation. In healthy individuals, isoUDCA fasting levels correlate with pre-meal appetite (p < 1 × 10-4). Our findings indicate an important role for isoUDCA in lipid metabolism, appetite, and, potentially, cardiometabolic risk.
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Affiliation(s)
- Panayiotis Louca
- Department of Twin Research & Genetic Epidemiology, King's College London, SE1 7EH London, UK
| | - Abraham S Meijnikman
- Department of (Experimental) Vascular Medicine, Amsterdam University Medical Centre (UMC), Amsterdam, the Netherlands
| | - Ana Nogal
- Department of Twin Research & Genetic Epidemiology, King's College London, SE1 7EH London, UK
| | | | - Ilias Attaye
- Department of (Experimental) Vascular Medicine, Amsterdam University Medical Centre (UMC), Amsterdam, the Netherlands
| | - Amrita Vijay
- Nottingham NIHR Biomedical Research Centre at the School of Medicine, University of Nottingham, NG5 1PB Nottingham, UK; Inflammation, Recovery and Injury Sciences, School of Medicine, University of Nottingham, NG5 1PB Nottingham, UK
| | - Afroditi Kouraki
- Nottingham NIHR Biomedical Research Centre at the School of Medicine, University of Nottingham, NG5 1PB Nottingham, UK; Inflammation, Recovery and Injury Sciences, School of Medicine, University of Nottingham, NG5 1PB Nottingham, UK
| | - Alessia Visconti
- Department of Twin Research & Genetic Epidemiology, King's College London, SE1 7EH London, UK
| | - Kari Wong
- Metabolon, Research Triangle Park, Morrisville, NC, USA
| | - Sarah E Berry
- Department of Nutritional Sciences, King's College London, London, UK
| | - Emily R Leeming
- Department of Twin Research & Genetic Epidemiology, King's College London, SE1 7EH London, UK
| | - Olatz Mompeo
- Department of Twin Research & Genetic Epidemiology, King's College London, SE1 7EH London, UK
| | - Francesca Tettamanzi
- Department of Twin Research & Genetic Epidemiology, King's College London, SE1 7EH London, UK
| | - Andrei-Florin Baleanu
- Department of Twin Research & Genetic Epidemiology, King's College London, SE1 7EH London, UK
| | - Mario Falchi
- Department of Twin Research & Genetic Epidemiology, King's College London, SE1 7EH London, UK
| | | | | | | | | | - Victor E A Gerdes
- Department of (Experimental) Vascular Medicine, Amsterdam University Medical Centre (UMC), Amsterdam, the Netherlands
| | | | - Paul W Franks
- Lund University Diabetes Center, Lund University, Malmö, Sweden; Department of Clinical Sciences, Lund University, Malmö, Sweden
| | - Nicola Segata
- Department CIBIO, University of Trento, Trento, Italy
| | - Massimo Mangino
- Department of Twin Research & Genetic Epidemiology, King's College London, SE1 7EH London, UK; NIHR Biomedical Research Centre at Guy's and St Thomas' Foundation Trust, SE1 9RT London, UK
| | - Tim D Spector
- Department of Twin Research & Genetic Epidemiology, King's College London, SE1 7EH London, UK
| | | | - Max Nieuwdorp
- Department of (Experimental) Vascular Medicine, Amsterdam University Medical Centre (UMC), Amsterdam, the Netherlands
| | - Ana M Valdes
- Nottingham NIHR Biomedical Research Centre at the School of Medicine, University of Nottingham, NG5 1PB Nottingham, UK; Inflammation, Recovery and Injury Sciences, School of Medicine, University of Nottingham, NG5 1PB Nottingham, UK.
| | - Cristina Menni
- Department of Twin Research & Genetic Epidemiology, King's College London, SE1 7EH London, UK.
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18
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Albaugh VL, Axelrod C, Belmont KP, Kirwan JP. Physiology Reconfigured: How Does Bariatric Surgery Lead to Diabetes Remission? Endocrinol Metab Clin North Am 2023; 52:49-64. [PMID: 36754497 DOI: 10.1016/j.ecl.2022.06.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Bariatric surgery improves glucose homeostasis and glycemic control in patients with type 2 diabetes. Over the past 20 years, a breadth of studies has been conducted in humans and rodents aimed to identify the regulatory nodes responsible for surgical remission of type 2 diabetes. The review herein discusses central mechanisms of type 2 diabetes remission associated with weight loss and surgical modification of the gastrointestinal tract.
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Affiliation(s)
- Vance L Albaugh
- Metamor Institute, Pennington Biomedical Research Center, 6400 Perkins Road, Baton Rouge, LA 70808, USA; Integrative Physiology and Molecular Medicine Laboratory, Pennington Biomedical Research Center, Louisiana State University, 6400 Perkins Road, Baton Rouge, LA 70808, USA
| | - Christopher Axelrod
- Integrative Physiology and Molecular Medicine Laboratory, Pennington Biomedical Research Center, Louisiana State University, 6400 Perkins Road, Baton Rouge, LA 70808, USA
| | - Kathryn P Belmont
- Integrative Physiology and Molecular Medicine Laboratory, Pennington Biomedical Research Center, Louisiana State University, 6400 Perkins Road, Baton Rouge, LA 70808, USA
| | - John P Kirwan
- Integrative Physiology and Molecular Medicine Laboratory, Pennington Biomedical Research Center, Louisiana State University, 6400 Perkins Road, Baton Rouge, LA 70808, USA.
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19
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Zheng Z, Hu Y, Tang J, Xu W, Zhu W, Zhang W. The implication of gut microbiota in recovery from gastrointestinal surgery. Front Cell Infect Microbiol 2023; 13:1110787. [PMID: 36926517 PMCID: PMC10011459 DOI: 10.3389/fcimb.2023.1110787] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Accepted: 02/15/2023] [Indexed: 03/08/2023] Open
Abstract
Recovery from gastrointestinal (GI) surgery is often interrupted by the unpredictable occurrence of postoperative complications, including infections, anastomotic leak, GI dysmotility, malabsorption, cancer development, and cancer recurrence, in which the implication of gut microbiota is beginning to emerge. Gut microbiota can be imbalanced before surgery due to the underlying disease and its treatment. The immediate preparations for GI surgery, including fasting, mechanical bowel cleaning, and antibiotic intervention, disrupt gut microbiota. Surgical removal of GI segments also perturbs gut microbiota due to GI tract reconstruction and epithelial barrier destruction. In return, the altered gut microbiota contributes to the occurrence of postoperative complications. Therefore, understanding how to balance the gut microbiota during the perioperative period is important for surgeons. We aim to overview the current knowledge to investigate the role of gut microbiota in recovery from GI surgery, focusing on the crosstalk between gut microbiota and host in the pathogenesis of postoperative complications. A comprehensive understanding of the postoperative response of the GI tract to the altered gut microbiota provides valuable cues for surgeons to preserve the beneficial functions and suppress the adverse effects of gut microbiota, which will help to enhance recovery from GI surgery.
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Affiliation(s)
| | | | | | | | | | - Wei Zhang
- Department of General Surgery, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
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20
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Mining the mechanistic underpinnings of bariatric surgery: A gateway to novel and non-invasive obesity therapies? Mol Metab 2023; 68:101663. [PMID: 36587843 PMCID: PMC9938305 DOI: 10.1016/j.molmet.2022.101663] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Revised: 12/16/2022] [Accepted: 12/22/2022] [Indexed: 12/30/2022] Open
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21
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Albaugh VL, He Y, Münzberg H, Morrison CD, Yu S, Berthoud HR. Regulation of body weight: Lessons learned from bariatric surgery. Mol Metab 2023; 68:101517. [PMID: 35644477 PMCID: PMC9938317 DOI: 10.1016/j.molmet.2022.101517] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2021] [Revised: 05/04/2022] [Accepted: 05/21/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Bariatric or weight loss surgery is currently the most effective treatment for obesity and metabolic disease. Unlike dieting and pharmacology, its beneficial effects are sustained over decades in most patients, and mortality is among the lowest for major surgery. Because there are not nearly enough surgeons to implement bariatric surgery on a global scale, intensive research efforts have begun to identify its mechanisms of action on a molecular level in order to replace surgery with targeted behavioral or pharmacological treatments. To date, however, there is no consensus as to the critical mechanisms involved. SCOPE OF REVIEW The purpose of this non-systematic review is to evaluate the existing evidence for specific molecular and inter-organ signaling pathways that play major roles in bariatric surgery-induced weight loss and metabolic benefits, with a focus on Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG), in both humans and rodents. MAJOR CONCLUSIONS Gut-brain communication and its brain targets of food intake control and energy balance regulation are complex and redundant. Although the relatively young science of bariatric surgery has generated a number of hypotheses, no clear and unique mechanism has yet emerged. It seems increasingly likely that the broad physiological and behavioral effects produced by bariatric surgery do not involve a single mechanism, but rather multiple signaling pathways. Besides a need to improve and better validate surgeries in animals, advanced techniques, including inducible, tissue-specific knockout models, and the use of humanized physiological traits will be necessary. State-of-the-art genetically-guided neural identification techniques should be used to more selectively manipulate function-specific pathways.
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Affiliation(s)
- Vance L Albaugh
- Translational and Integrative Gastrointestinal and Endocrine Research Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, USA
| | - Yanlin He
- Brain Glycemic and Metabolism Control Department, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, USA
| | - Heike Münzberg
- Neurobiology of Nutrition & Metabolism Department, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, USA
| | - Christopher D Morrison
- Neurobiology of Nutrition & Metabolism Department, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, USA
| | - Sangho Yu
- Neurobiology of Nutrition & Metabolism Department, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, USA
| | - Hans-Rudolf Berthoud
- Neurobiology of Nutrition & Metabolism Department, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, USA.
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22
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Feris F, McRae A, Kellogg TA, McKenzie T, Ghanem O, Acosta A. Mucosal and hormonal adaptations after Roux-en-Y gastric bypass. Surg Obes Relat Dis 2023; 19:37-49. [PMID: 36243547 PMCID: PMC9797451 DOI: 10.1016/j.soard.2022.08.020] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Revised: 08/26/2022] [Accepted: 08/30/2022] [Indexed: 01/12/2023]
Abstract
The aim of this study was to perform a comprehensive literature review regarding the relevant hormonal and histologic changes observed after Roux-en-Y gastric bypass (RYGB). We aimed to describe the relevant hormonal (glucagon-like peptides 1 and 2 [GLP-1 and GLP-2], peptide YY [PYY], oxyntomodulin [OXM], bile acids [BA], cholecystokinin [CCK], ghrelin, glucagon, gastric inhibitory polypeptide [GIP], and amylin) profiles, as well as the histologic (mucosal cellular) adaptations happening after patients undergo RYGB. Our review compiles the current evidence and furthers the understanding of the rationale behind the food intake regulatory adaptations occurring after RYGB surgery. We identify gaps in the literature where the potential for future investigations and therapeutics may lie. We performed a comprehensive database search without language restrictions looking for RYGB bariatric surgery outcomes in patients with pre- and postoperative blood work hormonal profiling and/or gut mucosal biopsies. We gathered the relevant study results and describe them in this review. Where human findings were lacking, we included animal model studies. The amalgamation of physiologic, metabolic, and cellular adaptations following RYGB is yet to be fully characterized. This constitutes a fundamental aspiration for enhancing and individualizing obesity therapy.
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Affiliation(s)
- Fauzi Feris
- Precision Medicine for Obesity Program, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota
| | - Alison McRae
- Precision Medicine for Obesity Program, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota
| | - Todd A Kellogg
- Division of Endocrine and Metabolic Surgery, Department of Surgery, Mayo Clinic, Rochester, Minnesota
| | - Travis McKenzie
- Division of Endocrine and Metabolic Surgery, Department of Surgery, Mayo Clinic, Rochester, Minnesota
| | - Omar Ghanem
- Division of Endocrine and Metabolic Surgery, Department of Surgery, Mayo Clinic, Rochester, Minnesota
| | - Andres Acosta
- Precision Medicine for Obesity Program, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota.
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23
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Giannini C, Mastromauro C, Scapaticci S, Gentile C, Chiarelli F. Role of bile acids in overweight and obese children and adolescents. Front Endocrinol (Lausanne) 2022; 13:1011994. [PMID: 36531484 PMCID: PMC9747777 DOI: 10.3389/fendo.2022.1011994] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Accepted: 11/07/2022] [Indexed: 12/05/2022] Open
Abstract
Bile acids (BAs) are amphipathic molecules synthetized in the liver. They are primarily involved in the digestion of nutrients. Apart from their role in dietary lipid absorption, BAs have progressively emerged as key regulators of systemic metabolism and inflammation. In the last decade, it became evident that BAs are particularly important for the regulation of glucose, lipid, and energy metabolism. Indeed, the interest in role of BA in metabolism homeostasis is further increased due to the global public health increase in obesity and related complications and a large number of research postulating that there is a close mutual relationship between BA and metabolic disorders. This strong relationship seems to derive from the role of BAs as signaling molecules involved in the regulation of a wide spectrum of metabolic pathways. These actions are mediated by different receptors, particularly nuclear farnesoid X receptor (FXR) and Takeda G protein coupled receptor 5 (TGR5), which are probably the major effectors of BA actions. These receptors activate transcriptional networks and signaling cascades controlling the expression and activity of genes involved in BA, lipid and carbohydrate metabolism, energy expenditure, and inflammation. The large correlation between BAs and metabolic disorders offers the possibility that modulation of BAs could be used as a therapeutic approach for the treatment of metabolic diseases, including obesity itself. The aim of this review is to describe the main physiological and metabolic actions of BA, focusing on its signaling pathways, which are important in the regulation of metabolism and might provide new BA -based treatments for metabolic diseases.
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Affiliation(s)
- Cosimo Giannini
- Department of Pediatrics, University of Chieti, Chieti, Italy
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24
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Fink J. In Reply. DEUTSCHES ARZTEBLATT INTERNATIONAL 2022; 119:610. [PMID: 36474343 PMCID: PMC9749839 DOI: 10.3238/arztebl.m2022.0179] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/05/2022]
Affiliation(s)
- Jodok Fink
- *Klinik für Allgemein- und Viszeralchirurgie Sektion für Adipositas und Metabolische Chirurgie Universitätsklinikum Freiburg
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25
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Cheng ZQ, Liu TM, Ren PF, Chen C, Wang YL, Dai Y, Zhang X. Duodenal-jejunal bypass reduces serum ceramides via inhibiting intestinal bile acid-farnesoid X receptor pathway. World J Gastroenterol 2022; 28:4328-4337. [PMID: 36159007 PMCID: PMC9453759 DOI: 10.3748/wjg.v28.i31.4328] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Revised: 05/12/2022] [Accepted: 07/25/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Bile acids play an important role in the amelioration of type 2 diabetes following duodenal-jejunal bypass (DJB). Serum bile acids are elevated postoperatively. However, the clinical relevance is not known. Bile acids in the peripheral circulation reflect the amount of bile acids in the gut. Therefore, a further investigation of luminal bile acids following DJB is of great significance.
AIM To investigate changes of luminal bile acids following DJB.
METHODS Salicylhydroxamic acid (SHAM), DJB, and DJB with oral chenodeoxycholic acid (CDCA) supplementation were performed in a high-fat-diet/streptozotocin-induced diabetic rat model. Body weight, energy intake, oral glucose tolerance test, luminal bile acids, serum ceramides and intestinal ceramide synthesis were analyzed at week 12 postoperatively.
RESULTS Compared to SHAM, DJB achieved rapid and durable improvement in glucose tolerance and led to increased total luminal bile acid concentrations with preferentially increased proportion of farnesoid X receptor (FXR) - inhibitory bile acids within the common limb. Intestinal ceramide synthesis was repressed with decreased serum ceramides, and this phenomenon could be partially antagonized by luminal supplementation of FXR activating bile acid CDCA.
CONCLUSION DJB significantly changes luminal bile acid composition with increased proportion FXR-inhibitory bile acids and reduces serum ceramide levels. There observations suggest a novel mechanism of bile acids in metabolic regulation after DJB.
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Affiliation(s)
- Zhi-Qiang Cheng
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
| | - Tong-Ming Liu
- Department of Colorectal and Anal Surgery, Feicheng Hospital Affiliated to Shandong First Medical University, Feicheng 271600, Shandong Province, China
| | - Peng-Fei Ren
- Department of General Surgery, Lincheng People’s Hospital, Dezhou 253500, Shandong Province, China
| | - Chang Chen
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
| | - Yan-Lei Wang
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
| | - Yong Dai
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
| | - Xiang Zhang
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
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26
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Sang M, Xie C, Qiu S, Wang X, Horowitz M, Jones KL, Rayner CK, Sun Z, Wu T. Cholecystectomy is associated with dysglycaemia: Cross-sectional and prospective analyses. Diabetes Obes Metab 2022; 24:1656-1660. [PMID: 35491529 PMCID: PMC9545089 DOI: 10.1111/dom.14730] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Revised: 04/09/2022] [Accepted: 04/26/2022] [Indexed: 12/30/2022]
Abstract
Cholecystectomy has been reported to be associated with increased risk of diabetes in cross-sectional studies. In the current study, we performed both cross-sectional and prospective analyses to examine the association between cholecystectomy and dysglycaemia in Chinese community-dwelling adults. A total of 1612 participants (n = 1564 without cholecystectomy and n = 48 with cholecystectomy) were evaluated for glycaemic status (according to the World Health Organization (WHO) 1999 criteria) and then followed up over ~3.2 years. Percent changes (Δ) in fasting blood glucose and HbA1c from baseline at the follow-up visit were calculated to define glycaemic control as stable (-10% ≤ Δ < 10%), improved (Δ < -10%), or worsened (Δ ≥ 10%). The baseline cross-sectional analyses indicated that cholecystectomy was associated with an increased risk of both prediabetes and diabetes, while the prospective analysis indicated that cholecystectomy was also associated with a greater risk of deterioration in glycaemic control (ΔFPG ≥10% and ΔHbA1c ≥10%) (P < 0.05 for each, both before and after adjusting for potential confounding covariates). These observations suggest that individuals in the Chinese community-dwelling population who have undergone cholecystectomy are at increased risk of dysglycaemia. Further studies are warranted to both delineate the underlying mechanisms and to clarify whether more intense surveillance for future development of diabetes is needed in this group.
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Affiliation(s)
- Miaomiao Sang
- Department of Endocrinology, Zhongda Hospital, Institute of Diabetes, School of MedicineSoutheast UniversityNanjingChina
| | - Cong Xie
- Centre of Research Excellence in Translating Nutritional Science to Good Health, Adelaide Medical SchoolThe University of AdelaideAdelaideSouth AustraliaAustralia
| | - Shanhu Qiu
- Department of General Practice, Zhongda Hospital, Institute of Diabetes, School of MedicineSoutheast UniversityNanjingChina
| | - Xuyi Wang
- Department of Clinical Nutrition, Zhongda Hospital, School of MedicineSoutheast UniversityNanjingChina
| | - Michael Horowitz
- Centre of Research Excellence in Translating Nutritional Science to Good Health, Adelaide Medical SchoolThe University of AdelaideAdelaideSouth AustraliaAustralia
- Endocrine and Metabolic UnitRoyal Adelaide HospitalAdelaideSouth AustraliaAustralia
| | - Karen L. Jones
- Centre of Research Excellence in Translating Nutritional Science to Good Health, Adelaide Medical SchoolThe University of AdelaideAdelaideSouth AustraliaAustralia
- Endocrine and Metabolic UnitRoyal Adelaide HospitalAdelaideSouth AustraliaAustralia
| | - Christopher K. Rayner
- Centre of Research Excellence in Translating Nutritional Science to Good Health, Adelaide Medical SchoolThe University of AdelaideAdelaideSouth AustraliaAustralia
- Department of Gastroenterology and HepatologyRoyal Adelaide HospitalAdelaideSouth AustraliaAustralia
| | - Zilin Sun
- Department of Endocrinology, Zhongda Hospital, Institute of Diabetes, School of MedicineSoutheast UniversityNanjingChina
| | - Tongzhi Wu
- Centre of Research Excellence in Translating Nutritional Science to Good Health, Adelaide Medical SchoolThe University of AdelaideAdelaideSouth AustraliaAustralia
- Endocrine and Metabolic UnitRoyal Adelaide HospitalAdelaideSouth AustraliaAustralia
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27
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Zheng Z, Pang Q, Luo X, Tao F, Duan J, Cao J. The Role of Bile Acid in Improving Glucose Tolerance of Non-Obese Diabetic Rats After Proximal Small Bowel Bypass. Front Physiol 2022; 13:878505. [PMID: 35784867 PMCID: PMC9243444 DOI: 10.3389/fphys.2022.878505] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2022] [Accepted: 05/26/2022] [Indexed: 11/13/2022] Open
Abstract
An increase in bile acid (BA) levels after metabolic surgery is an important mechanism for improving glucose metabolism. However, the mechanisms underlying elevated BA levels and the regulatory mechanism of glucose metabolism remain unclear. In this study, we used the Goto-Kakizaki rat model to investigate the mechanism of BA elevation by comparing side-to-side jejunoileal bypass plus proximal loop ligation (SSJIBL) and bile ileum diversion (BID) as well as to explore the mechanism of BA metabolism in regulating blood glucose. The results showed that the fed blood glucose of rats in both the SSJIBL and BID groups was significantly lower than that of the SHAM group on days 2 and 14 after the operation. The oral glucose tolerance test (OGTT) improved in the SSJIBL and BID groups at day 14 postoperatively. The expression of CYP27A1 in the livers of the SSJIBL and BID groups was significantly increased. In addition, total serum BA levels in the SSJIBL and BID groups were significantly increased. Moreover, serum levels of lithocholic acid (LCA) and deoxycholic acid (DCA) were significantly higher in the SSJIBL group than in the SHAM group and negatively correlated with the area under the glucose tolerance curve (AUC-OGTT). In conclusion, increased BA synthesis may be an important cause of elevated total serum BA levels, and LCA and DCA are closely associated with improved glucose metabolism.
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Affiliation(s)
- Zhihua Zheng
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Qiang Pang
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Xin Luo
- Department of General Surgery, Gastrointestinal Surgical Institute of Nanchang University, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Fang Tao
- Department of General Surgery, Gastrointestinal Surgical Institute of Nanchang University, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Jinyuan Duan
- Department of General Surgery, Gastrointestinal Surgical Institute of Nanchang University, The First Affiliated Hospital of Nanchang University, Nanchang, China
- *Correspondence: Jinyuan Duan, ; Jiaqing Cao,
| | - Jiaqing Cao
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
- *Correspondence: Jinyuan Duan, ; Jiaqing Cao,
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28
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Wang X, Chen C, Xie C, Huang W, Young RL, Jones KL, Horowitz M, Rayner CK, Sun Z, Wu T. Serum bile acid response to oral glucose is attenuated in patients with early type 2 diabetes and correlates with 2-hour plasma glucose in individuals without diabetes. Diabetes Obes Metab 2022; 24:1132-1142. [PMID: 35238131 PMCID: PMC9540586 DOI: 10.1111/dom.14683] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Revised: 02/21/2022] [Accepted: 03/01/2022] [Indexed: 12/13/2022]
Abstract
AIM To determine the serum bile acid (BA) response to 75-g oral glucose in individuals without diabetes, and whether this is attenuated in patients with 'early' type 2 diabetes (T2D) and related to the glycaemic response at 2 hours in either group. METHODS Forty newly diagnosed, treatment-naïve Han Chinese T2D subjects and 40 age-, gender-, and body mass index-matched controls without T2D ingested a 75-g glucose drink after an overnight fast. Plasma glucose and serum concentrations of total and individual BAs, fibroblast growth factor-19 (FGF-19), total glucagon-like peptide-1 (GLP-1), and insulin, were measured before and 2 hours after oral glucose. RESULTS Fasting total BA levels were higher in T2D than control subjects (P < .05). At 2 hours, the BA profile exhibited a shift from baseline in both groups, with increases in conjugated BAs and/or decreases in unconjugated BAs. There were increases in total BA and FGF-19 levels in control (both P < .05), but not T2D, subjects. Plasma glucose concentrations at 2 hours related inversely to serum total BA levels in control subjects (r = -0.42, P = .006). Total GLP-1 and the insulin/glucose ratio were increased at 2 hours in both groups, and the magnitude of the increase was greater in control subjects. CONCLUSIONS The serum BA response to a 75-g oral glucose load is attenuated in patients with 'early' T2D, as is the secretion of FGF-19 and GLP-1, while in individuals without T2D it correlates with 2-hour plasma glucose levels. These observations support a role for BAs in the regulation of postprandial glucose metabolism.
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Affiliation(s)
- Xuyi Wang
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good HealthThe University of AdelaideAdelaide
- Department of Clinical NutritionSoutheast UniversityNanjingChina
| | - Chang Chen
- Institute of Life SciencesChongqing Medical UniversityChongqingChina
| | - Cong Xie
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good HealthThe University of AdelaideAdelaide
| | - Weikun Huang
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good HealthThe University of AdelaideAdelaide
| | - Richard L. Young
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good HealthThe University of AdelaideAdelaide
- Nutrition, Diabetes & Gut Health, Lifelong Health ThemeSouth Australian Health & Medical Research InstituteAdelaideAustralia
| | - Karen L. Jones
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good HealthThe University of AdelaideAdelaide
- Endocrine and Metabolic UnitRoyal Adelaide HospitalAdelaide
| | - Michael Horowitz
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good HealthThe University of AdelaideAdelaide
- Endocrine and Metabolic UnitRoyal Adelaide HospitalAdelaide
| | - Christopher K. Rayner
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good HealthThe University of AdelaideAdelaide
- Department of Gastroenterology and HepatologyRoyal Adelaide HospitalAdelaideAustralia
| | - Zilin Sun
- Department of Endocrinology, Zhongda Hospital, Institute of Diabetes, School of MedicineSoutheast UniversityNanjing
| | - Tongzhi Wu
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good HealthThe University of AdelaideAdelaide
- Endocrine and Metabolic UnitRoyal Adelaide HospitalAdelaide
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29
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Fénelon VS, Cota D. [Hypothalamic bile acid-TGR5 signaling: A therapeutic target in the fight against obesity?]. Med Sci (Paris) 2022; 38:413-415. [PMID: 35608459 DOI: 10.1051/medsci/2022052] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Affiliation(s)
- Valérie S Fénelon
- Université de Bordeaux, Inserm U1215, Neurocentre Magendie, Bordeaux, France
| | - Daniela Cota
- Université de Bordeaux, Inserm U1215, Neurocentre Magendie, Bordeaux, France
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30
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Fries CM, Haange SB, Rolle-Kampczyk U, Till A, Lammert M, Grasser L, Medawar E, Dietrich A, Horstmann A, von Bergen M, Fenske WK. Metabolic Profile and Metabolite Analyses in Extreme Weight Responders to Gastric Bypass Surgery. Metabolites 2022; 12:metabo12050417. [PMID: 35629921 PMCID: PMC9147451 DOI: 10.3390/metabo12050417] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Revised: 04/26/2022] [Accepted: 04/29/2022] [Indexed: 11/16/2022] Open
Abstract
Background: Roux-en-Y gastric bypass (RYGB) surgery belongs to the most frequently performed surgical therapeutic strategies against adiposity and its comorbidities. However, outcome is limited in a substantial cohort of patients with inadequate primary weight loss or considerable weight regain. In this study, gut microbiota composition and systemically released metabolites were analyzed in a cohort of extreme weight responders after RYGB. Methods: Patients (n = 23) were categorized based on excess weight loss (EWL) at a minimum of two years after RYGB in a good responder (EWL 93 ± 4.3%) or a bad responder group (EWL 19.5 ± 13.3%) for evaluation of differences in metabolic outcome, eating behavior and gut microbiota taxonomy and metabolic activity. Results: Mean BMI was 47.2 ± 6.4 kg/m2 in the bad vs. 26.6 ± 1.2 kg/m2 in the good responder group (p = 0.0001). We found no difference in hunger and satiety sensation, in fasting or postprandial gut hormone release, or in gut microbiota composition between both groups. Differences in weight loss did not reflect in metabolic outcome after RYGB. While fecal and circulating metabolite analyses showed higher levels of propionate (p = 0.0001) in good and valerate (p = 0.04) in bad responders, respectively, conjugated primary and secondary bile acids were higher in good responders in the fasted (p = 0.03) and postprandial state (GCA, p = 0.02; GCDCA, p = 0.02; TCA, p = 0.01; TCDCA, p = 0.02; GDCA, p = 0.05; GUDCA, p = 0.04; TLCA, p = 0.04). Conclusions: Heterogenous weight loss response to RYGB surgery separates from patients’ metabolic outcome, and is linked to unique serum metabolite signatures post intervention. These findings suggest that the level of adiposity reduction alone is insufficient to assess the metabolic success of RYGB surgery, and that longitudinal metabolite profiling may eventually help us to identify markers that could predict individual adiposity response to surgery and guide patient selection and counseling.
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Affiliation(s)
- Charlotte M. Fries
- Department of Endocrinology, Diabetes and Metabolism, University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany; (A.T.); (W.K.F.)
- Correspondence:
| | - Sven-Bastiaan Haange
- Department of Molecular Systems Biology, Helmholtz Centre for Environmental Research GmbH-UFZ, Permoserstraße 15, 04318 Leipzig, Germany; (S.-B.H.); (U.R.-K.); (M.v.B.)
| | - Ulrike Rolle-Kampczyk
- Department of Molecular Systems Biology, Helmholtz Centre for Environmental Research GmbH-UFZ, Permoserstraße 15, 04318 Leipzig, Germany; (S.-B.H.); (U.R.-K.); (M.v.B.)
| | - Andreas Till
- Department of Endocrinology, Diabetes and Metabolism, University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany; (A.T.); (W.K.F.)
| | - Mathis Lammert
- Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Stephanstraße 1a, 04103 Leipzig, Germany; (M.L.); (L.G.); (E.M.); (A.H.)
| | - Linda Grasser
- Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Stephanstraße 1a, 04103 Leipzig, Germany; (M.L.); (L.G.); (E.M.); (A.H.)
| | - Evelyn Medawar
- Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Stephanstraße 1a, 04103 Leipzig, Germany; (M.L.); (L.G.); (E.M.); (A.H.)
| | - Arne Dietrich
- Department of Visceral and Metabolic Surgery, University Hospital Leipzig, Liebigstraße 18, 04103 Leipzig, Germany;
| | - Annette Horstmann
- Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Stephanstraße 1a, 04103 Leipzig, Germany; (M.L.); (L.G.); (E.M.); (A.H.)
- Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Haartmaninkatu 3, 00290 Helsinki, Finland
| | - Martin von Bergen
- Department of Molecular Systems Biology, Helmholtz Centre for Environmental Research GmbH-UFZ, Permoserstraße 15, 04318 Leipzig, Germany; (S.-B.H.); (U.R.-K.); (M.v.B.)
- German Centre for Integrative Biodiversity Research (iDiv) Halle-Jena-Leipzig, Puschstraße 4, 04103 Leipzig, Germany
- Faculty of Life Sciences, Institute of Biochemistry, University of Leipzig, Brüderstraße 34, 04103 Leipzig, Germany
| | - Wiebke K. Fenske
- Department of Endocrinology, Diabetes and Metabolism, University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany; (A.T.); (W.K.F.)
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31
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Combined liver transplantation with sleeve gastrectomy: a pioneer case series from Brazil. Updates Surg 2022; 74:81-86. [PMID: 35103918 DOI: 10.1007/s13304-021-01230-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Accepted: 12/23/2021] [Indexed: 02/07/2023]
Abstract
The association of a bariatric operation during liver transplantation may benefit patients with liver failure and obesity and sleeve gastrectomy emerges as the procedure of choice. The aim of this study is to present our experience with combined liver transplantation and sleeve gastrectomy. During an 18-month period, seven patients were submitted to simultaneous liver transplant and sleeve gastrectomy (LTSG). There were four male and three female, and the mean recipient age was 60.5 years, mean BMI was 38.2 kg/m2, and mean MELD score was 25 points. The indication for liver transplantation was nonalcoholic steatohepatitis (NASH) with hepatocellular carcinoma (HCC) in four cases, hepatitis C with HCC in one case, pure NASH in one case and alcoholic cirrhosis with HCC in one case. Six patients are alive with normal allograft function. There were no biliary complications.
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32
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Seyfried F, Phetcharaburanin J, Glymenaki M, Nordbeck A, Hankir M, Nicholson JK, Holmes E, Marchesi JR, Li JV. Roux-en-Y gastric bypass surgery in Zucker rats induces bacterial and systemic metabolic changes independent of caloric restriction-induced weight loss. Gut Microbes 2022; 13:1-20. [PMID: 33535876 PMCID: PMC7872092 DOI: 10.1080/19490976.2021.1875108] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
Mechanisms of Roux-en-Y gastric bypass (RYGB) surgery are not fully understood. This study aimed to investigate weight loss-independent bacterial and metabolic changes, as well as the absorption of bacterial metabolites and bile acids through the hepatic portal system following RYGB surgery. Three groups of obese Zucker (fa/fa) rats were included: RYGB (n = 11), sham surgery and body weight matched with RYGB (Sham-BWM, n = 5), and sham surgery fed ad libitum (Sham-obese, n = 5). Urine and feces were collected at multiple time points, with portal vein and peripheral blood obtained at the end of the study. Metabolic phenotyping approaches and 16S rRNA gene sequencing were used to determine the biochemical and bacterial composition of the samples, respectively. RYGB surgery-induced distinct metabolic and bacterial disturbances, which were independent of weight loss through caloric restriction. RYGB resulted in lower absorption of phenylalanine and choline, and higher urinary concentrations of host-bacterial co-metabolites (e.g., phenylacetylglycine, indoxyl sulfate), together with higher fecal trimethylamine, suggesting enhanced bacterial aromatic amino acid and choline metabolism. Short chain fatty acids (SCFAs) were lower in feces and portal vein blood from RYGB group compared to Sham-BWM, accompanied with lower abundances of Lactobacillaceae, and Ruminococcaceae known to contain SCFA producers, indicating reduced bacterial fiber fermentation. Fecal γ-amino butyric acid (GABA) was found in higher concentrations in RYGB than that in Sham groups and could play a role in the metabolic benefits associated with RYGB surgery. While no significant difference in urinary BA excretion, RYGB lowered both portal vein and circulating BA compared to Sham groups. These findings provide a valuable resource for how dynamic, multi-systems changes impact on overall metabolic health, and may provide potential therapeutic targets for developing downstream non-surgical treatment for metabolic disease.
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Affiliation(s)
- Florian Seyfried
- Department of General, Visceral, Transplant, Vascular, and Pediatric Surgery, University Hospital Wuerzburg, Wuerzburg, Germany
| | - Jutarop Phetcharaburanin
- Department of Metabolism Digestion and Reproduction, Faculty of Medicine, Imperial College LondonLondon, UK,Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Maria Glymenaki
- Department of Metabolism Digestion and Reproduction, Faculty of Medicine, Imperial College LondonLondon, UK
| | - Arno Nordbeck
- Department of General, Visceral, Transplant, Vascular, and Pediatric Surgery, University Hospital Wuerzburg, Wuerzburg, Germany
| | - Mohammed Hankir
- Department of General, Visceral, Transplant, Vascular, and Pediatric Surgery, University Hospital Wuerzburg, Wuerzburg, Germany
| | - Jeremy K Nicholson
- Division of Organisms and Environment, School of Biosciences, Institute of Health Futures, Murdoch University, Perth, Western Australia, Australia
| | - Elaine Holmes
- Department of Metabolism Digestion and Reproduction, Faculty of Medicine, Imperial College LondonLondon, UK,Division of Organisms and Environment, School of Biosciences, Institute of Health Futures, Murdoch University, Perth, Western Australia, Australia
| | - Julian R. Marchesi
- Department of Metabolism Digestion and Reproduction, Faculty of Medicine, Imperial College LondonLondon, UK,School of Biosciences, Cardiff University, Cardiff, UK
| | - Jia V. Li
- Department of Metabolism Digestion and Reproduction, Faculty of Medicine, Imperial College LondonLondon, UK,CONTACT Jia V. Li Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, United Kingdom
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33
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Oh JH, Kang CW, Wang EK, Nam JH, Lee S, Park KH, Lee EJ, Cho A, Ku CR. Altered Glucose Metabolism and Glucose Transporters in Systemic Organs After Bariatric Surgery. Front Endocrinol (Lausanne) 2022; 13:937394. [PMID: 35909546 PMCID: PMC9329688 DOI: 10.3389/fendo.2022.937394] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Accepted: 06/20/2022] [Indexed: 11/13/2022] Open
Abstract
The Roux-en-Y gastric bypass (RYGB) is highly effective in the remission of obesity and associated diabetes. The mechanisms underlying obesity and type 2 diabetes mellitus remission after RYGB remain unclear. This study aimed to evaluate the changes in continuous dynamic FDG uptake patterns after RYGB and examine the correlation between glucose metabolism and its transporters in variable endocrine organs using 18F-fluoro-2-deoxyglucose positron emission tomography images. Increased glucose metabolism in specific organs, such as the small intestine and various fat tissues, is closely associated with improved glycemic control after RYGB. In Otsuka Long-Evans Tokushima Fatty rats fed with high-fat diets, RYGB operation increases intestine glucose transporter expression and various fat tissues' glucose transporters, which are not affected by insulin. The fasting glucose decrement was significantly associated with RYGB, sustained weight loss, post-RYGB oral glucose tolerance test (OGTT) area under the curve (AUC), glucose transporter, or glycolytic enzymes in the small bowel and various fat tissues. High intestinal glucose metabolism and white adipose tissue-dependent glucose metabolism correlated with metabolic benefit after RYGB. These findings suggest that the newly developed glucose biodistribution accompanied by increased glucose transporters is a mechanism associated with the systemic effect of RYGB.
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Affiliation(s)
- Ju Hun Oh
- Brain Korea 21 PLUS Project for Medical Science, Yonsei University, College of Medicine, Seoul, South Korea
- Department of Internal Medicine, Endocrinology, Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, South Korea
| | - Chan Woo Kang
- Department of Internal Medicine, Endocrinology, Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, South Korea
| | - Eun Kyung Wang
- Department of Internal Medicine, Endocrinology, Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, South Korea
| | - Jung Ho Nam
- Brain Korea 21 PLUS Project for Medical Science, Yonsei University, College of Medicine, Seoul, South Korea
- Department of Internal Medicine, Endocrinology, Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, South Korea
| | - Soohyun Lee
- Department of Internal Medicine, Endocrinology, Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, South Korea
| | - Kyeong Hye Park
- Division of Endocrinology and Metabolism, Department of Internal Medicine, National Health Insurance Service Ilsan Hospital, Goyang, South Korea
| | - Eun Jig Lee
- Department of Internal Medicine, Endocrinology, Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, South Korea
| | - Arthur Cho
- Department of Nuclear Medicine, Yonsei University College of Medicine, Seoul, South Korea
- *Correspondence: Cheol Ryong Ku, ; Arthur Cho,
| | - Cheol Ryong Ku
- Department of Internal Medicine, Endocrinology, Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, South Korea
- *Correspondence: Cheol Ryong Ku, ; Arthur Cho,
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Zhou S, Chen W, Bai X, Chen J, Xu Q, Dong L, Chen W, Qu Q, He X. Upregulation of hypothalamic POMC neurons after biliary diversion in GK rats. Front Endocrinol (Lausanne) 2022; 13:999928. [PMID: 36277690 PMCID: PMC9585246 DOI: 10.3389/fendo.2022.999928] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2022] [Accepted: 09/16/2022] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Bile acids are important signaling molecules that might activate hypothalamic neurons. This study aimed to investigate possible changes in hypothalamic pro-opiomelanocortin (POMC) neurons after biliary diversion in diabetic rats. METHODS Ten GK rats were randomly divided into the biliary diversion (BD) and sham groups. The glucose metabolism, hypothalamic POMC expression, serum bile acid profiles, and ileal bile acid-specific receptors of the two groups were analyzed. RESULTS Biliary diversion improved blood glucose (P = 0.001) and glucose tolerance (P = 0.001). RNA-Seq of the hypothalamus showed significantly upregulated expression of the POMC gene (log2-fold change = 4.1, P < 0.001), which also showed increased expression at the protein (P = 0.030) and mRNA (P = 0.004) levels. The POMC-derived neuropeptide α-melanocyte stimulating hormone (α-MSH) was also increased in the hypothalamus (2.21 ± 0.11 ng/g, P = 0.006). In addition, increased taurocholic acid (TCA) (108.05 ± 20.62 ng/mL, P = 0.003) and taurodeoxycholic acid (TDCA) (45.58 ± 2.74 ng/mL, P < 0.001) were found in the BD group and induced the enhanced secretion of fibroblast growth factor-15 (FGF15, 74.28 ± 3.44 pg/ml, P = 0.001) by activating farnesoid X receptor (FXR) that was over-expressed in the ileum. CONCLUSIONS Hypothalamic POMC neurons were upregulated after BD, and the increased TCA, TDCA, and the downstream gut-derived hormone FGF15 might activate POMC neurons.
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Affiliation(s)
- Shengnan Zhou
- Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, China Academy of Medical Science & Peking Union Medical College, Beijing, China
| | - Weijie Chen
- Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, China Academy of Medical Science & Peking Union Medical College, Beijing, China
| | - Xuesong Bai
- Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, China Academy of Medical Science & Peking Union Medical College, Beijing, China
| | - Jiemin Chen
- Gastroenterology Department, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, China Academy of Medical Science & Peking Union Medical College, Beijing, China
| | - Qiang Xu
- Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, China Academy of Medical Science & Peking Union Medical College, Beijing, China
| | - Liangbo Dong
- Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, China Academy of Medical Science & Peking Union Medical College, Beijing, China
| | - Wei Chen
- Clinical Nutrition Department, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, China Academy of Medical Science & Peking Union Medical College, Beijing, China
| | - Qiang Qu
- Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, China Academy of Medical Science & Peking Union Medical College, Beijing, China
| | - Xiaodong He
- Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, China Academy of Medical Science & Peking Union Medical College, Beijing, China
- *Correspondence: Xiaodong He,
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Kwon IG, Kang CW, Park JP, Oh JH, Wang EK, Kim TY, Sung JS, Park N, Lee YJ, Sung HJ, Lee EJ, Hyung WJ, Shin SJ, Noh SH, Yun M, Kang WJ, Cho A, Ku CR. Serum glucose excretion after Roux-en-Y gastric bypass: a potential target for diabetes treatment. Gut 2021; 70:1847-1856. [PMID: 33208408 DOI: 10.1136/gutjnl-2020-321402] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2020] [Revised: 11/04/2020] [Accepted: 11/05/2020] [Indexed: 12/12/2022]
Abstract
OBJECTIVE The mechanisms underlying type 2 diabetes resolution after Roux-en-Y gastric bypass (RYGB) are unclear. We suspected that glucose excretion may occur in the small bowel based on observations in humans. The aim of this study was to evaluate the mechanisms underlying serum glucose excretion in the small intestine and its contribution to glucose homeostasis after bariatric surgery. DESIGN 2-Deoxy-2-[18F]-fluoro-D-glucose (FDG) was measured in RYGB-operated or sham-operated obese diabetic rats. Altered glucose metabolism was targeted and RNA sequencing was performed in areas of high or low FDG uptake in the ileum or common limb. Intestinal glucose metabolism and excretion were confirmed using 14C-glucose and FDG. Increased glucose metabolism was evaluated in IEC-18 cells and mouse intestinal organoids. Obese or ob/ob mice were treated with amphiregulin (AREG) to correlate intestinal glycolysis changes with changes in serum glucose homeostasis. RESULTS The AREG/EGFR/mTOR/AKT/GLUT1 signal transduction pathway was activated in areas of increased glycolysis and intestinal glucose excretion in RYGB-operated rats. Intraluminal GLUT1 inhibitor administration offset improved glucose homeostasis in RYGB-operated rats. AREG-induced signal transduction pathway was confirmed using IEC-18 cells and mouse organoids, resulting in a greater capacity for glucose uptake via GLUT1 overexpression and sequestration in apical and basolateral membranes. Systemic and local AREG administration increased GLUT1 expression and small intestinal membrane translocation and prevented hyperglycaemic exacerbation. CONCLUSION Bariatric surgery or AREG administration induces apical and basolateral membrane GLUT1 expression in the small intestinal enterocytes, resulting in increased serum glucose excretion in the gut lumen. Our findings suggest a novel, potentially targetable glucose homeostatic mechanism in the small intestine.
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Affiliation(s)
- In Gyu Kwon
- Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Chan Woo Kang
- Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, Republic of Korea
| | - Jong-Pil Park
- Department of Forensic Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Ju Hun Oh
- Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, Republic of Korea.,Endocrinology, Institute of Endocrine Research, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Eun Kyung Wang
- Endocrinology, Institute of Endocrine Research, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Tae Young Kim
- Department of Medical Engineering, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jin Sol Sung
- Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, Republic of Korea
| | - Namhee Park
- Department of Nuclear Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Yang Jong Lee
- Endocrinology, Institute of Endocrine Research, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hak-Joon Sung
- Department of Medical Engineering, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Eun Jig Lee
- Endocrinology, Institute of Endocrine Research, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Woo Jin Hyung
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Su-Jin Shin
- Department of Pathology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Sung Hoon Noh
- Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Mijin Yun
- Department of Nuclear Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Won Jun Kang
- Department of Nuclear Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Arthur Cho
- Department of Nuclear Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Cheol Ryong Ku
- Endocrinology, Institute of Endocrine Research, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
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Albaugh VL. Comment on: The effect of sleeve ablation of gastric mucosa on body weight and glucose homeostasis in the rat. Surg Obes Relat Dis 2021; 17:1994-1995. [PMID: 34561170 DOI: 10.1016/j.soard.2021.08.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Accepted: 08/21/2021] [Indexed: 10/20/2022]
Affiliation(s)
- Vance L Albaugh
- Assistant Professor of Metabolic Surgery, Pennington Biomedical Research Center, Baton Rouge, Louisiana
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Lefere S, Onghena L, Vanlander A, van Nieuwenhove Y, Devisscher L, Geerts A. Bariatric surgery and the liver-Mechanisms, benefits, and risks. Obes Rev 2021; 22:e13294. [PMID: 34002452 DOI: 10.1111/obr.13294] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2021] [Revised: 05/01/2021] [Accepted: 05/03/2021] [Indexed: 12/18/2022]
Abstract
The prevalence of obesity and metabolic diseases such as type 2 diabetes and nonalcoholic fatty liver disease (NAFLD) has risen dramatically over the past decades. At present, bariatric surgery is the most effective treatment for this global health problem, through effects on food intake, gut hormone secretion, metabolic signaling pathways, and adipose tissue dysfunction. The liver occupies a central role in carbohydrate, protein, and lipid metabolism. Notably, a reduction in hepatic fat content and an improvement in hepatic insulin resistance are among the earliest beneficial effects of bariatric surgery, which has therefore emerged as an attractive treatment option for NAFLD. However, as the scope and popularity of weight loss surgery have expanded, new questions have arisen regarding its safety in patients with liver cirrhosis, the outcome of liver transplantation in patients with a history of bariatric surgery, and over incidental reports of liver failure following surgery. Studies in humans and rodents have also linked bariatric surgery to an increased risk of developing alcohol use disorder, a major risk factor for liver disease. This review integrates data from clinical and translational research to delineate both the beneficial impact of bariatric surgery on the liver and the potential risks involved.
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Affiliation(s)
- Sander Lefere
- Hepatology Research Unit, Department of Internal Medicine and Pediatrics, Liver Research Center Ghent, Ghent University, Ghent, Belgium.,Gut-Liver Immunopharmacology Unit, Department of Basic and Applied Medical Sciences, Liver Research Center Ghent, Ghent University, Ghent, Belgium
| | - Louis Onghena
- Department of Gastrointestinal Surgery, Ghent University, Ghent, Belgium.,Department of General and Hepatobiliary Surgery, Liver Transplantation Service, Ghent University, Ghent, Belgium
| | - Aude Vanlander
- Department of General and Hepatobiliary Surgery, Liver Transplantation Service, Ghent University, Ghent, Belgium
| | | | - Lindsey Devisscher
- Gut-Liver Immunopharmacology Unit, Department of Basic and Applied Medical Sciences, Liver Research Center Ghent, Ghent University, Ghent, Belgium
| | - Anja Geerts
- Hepatology Research Unit, Department of Internal Medicine and Pediatrics, Liver Research Center Ghent, Ghent University, Ghent, Belgium
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Lee G, Park YS, Cho C, Lee H, Park J, Park DJ, Lee JH, Lee HJ, Ha TK, Kim YJ, Ryu SW, Han SM, Yoo MW, Park S, Han SU, Heo Y, Jung BH. Short-term changes in the serum metabolome after laparoscopic sleeve gastrectomy and Roux-en-Y gastric bypass. Metabolomics 2021; 17:71. [PMID: 34355282 DOI: 10.1007/s11306-021-01826-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Accepted: 07/27/2021] [Indexed: 11/30/2022]
Abstract
INTRODUCTION Bariatric surgery is known to be the most effective treatment for weight loss in obese patients and for the rapid remission of obesity-related comorbidities. These short-term improvements result from not only limited digestion or absorption but also dynamic changes in metabolism throughout the whole body. However, short-term metabolism studies associated with bariatric surgery in Asian individuals have not been reported. OBJECTIVES The aim of this study was to investigate the short-term metabolome changes in the serum promoted by laparoscopic sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) and to determine the underlying mechanisms that affect obesity-related comorbidities. METHODS Serum samples were collected from Korean patients who underwent RYGB or SG before and 4 weeks after the surgery. Metabolomic and lipidomic profiling was performed using UPLC-Orbitrap-MS, and data were analyzed using statistical analysis. RESULTS Metabolites mainly related to amino acids, lipids (fatty acids, glycerophospholipids, sphingolipids, glycerolipids) and bile acids changed after surgery, and these changes were associated with the lowering of risk factors for obesity-related diseases such as nonalcoholic fatty liver disease (NAFLD), type 2 diabetes (T2D) and atherosclerosis. Interestingly, the number of significantly altered metabolites related to the lipid metabolism were greater in SG than in RYGB. Furthermore, the metabolites related to amino acid metabolism were significantly changed only after SG, whereas bile acid changed significantly only following RYGB. CONCLUSION These differences could result from anatomical differences between the two surgeries and could be related to the gut microbiota. This study provides crucial information to expand the knowledge of the common but different molecular mechanisms involved in obesity and obesity-related comorbidities affected by each bariatric procedure.
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Affiliation(s)
- Gakyung Lee
- Molecular Recognition Research Center, Korea Institute of Science and Technology (KIST), Hwarangno 14-gil 5, Seongbuk-gu, Seoul, 02792, Republic of Korea
- Division of Bio-Medical Science and Technology, KIST-School, Korea University of Science and Technology (UST), Seoul, Republic of Korea
| | - Young Suk Park
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Chamlee Cho
- Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University, Samsung Medical Center, Seoul, Republic of Korea
| | - Hyunbeom Lee
- Molecular Recognition Research Center, Korea Institute of Science and Technology (KIST), Hwarangno 14-gil 5, Seongbuk-gu, Seoul, 02792, Republic of Korea
| | - Jinyoung Park
- Molecular Recognition Research Center, Korea Institute of Science and Technology (KIST), Hwarangno 14-gil 5, Seongbuk-gu, Seoul, 02792, Republic of Korea
| | - Do Joong Park
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
- Department of Surgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - Joo Ho Lee
- Department of Surgery, Nowon Eulji Medical Center, Eulji University, Seoul, Republic of Korea
| | - Hyuk-Joon Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - Tae Kyung Ha
- Department of Surgery, Hanyang University College of Medicine, Seoul, Republic of Korea
| | - Yong-Jin Kim
- Department of Surgery, Soonchunhyang University Hospital, Seoul, Republic of Korea
- Department of Surgery, H+ Yangji Hospital, Seoul, Republic of Korea
| | - Seung-Wan Ryu
- Department of Surgery, Keimyung University Dongsan Hospital, Daegu, Republic of Korea
| | - Sang-Moon Han
- Department of Surgery, CHA Gangnam Medical Center, Seoul, Republic of Korea
- Department of Surgery, Cheil General Hospital, Seoul, Republic of Korea
| | - Moon-Won Yoo
- Department of Surgery, Asan Medical Center, Seoul, Republic of Korea
| | - Sungsoo Park
- Department of Surgery, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Republic of Korea
| | - Sang-Uk Han
- Department of Surgery, Ajou University Hospital, Suwon, Republic of Korea
| | - Yoonseok Heo
- Department of Surgery, Inha University Hospital, Incheon, Republic of Korea
| | - Byung Hwa Jung
- Molecular Recognition Research Center, Korea Institute of Science and Technology (KIST), Hwarangno 14-gil 5, Seongbuk-gu, Seoul, 02792, Republic of Korea.
- Division of Bio-Medical Science and Technology, KIST-School, Korea University of Science and Technology (UST), Seoul, Republic of Korea.
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Sauerbruch T, Hennenberg M, Trebicka J, Beuers U. Bile Acids, Liver Cirrhosis, and Extrahepatic Vascular Dysfunction. Front Physiol 2021; 12:718783. [PMID: 34393832 PMCID: PMC8358446 DOI: 10.3389/fphys.2021.718783] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Accepted: 06/29/2021] [Indexed: 12/12/2022] Open
Abstract
The bile acid pool with its individual bile acids (BA) is modulated in the enterohepatic circulation by the liver as the primary site of synthesis, the motility of the gallbladder and of the intestinal tract, as well as by bacterial enzymes in the intestine. The nuclear receptor farnesoid X receptor (FXR) and Gpbar1 (TGR5) are important set screws in this process. Bile acids have a vasodilatory effect, at least according to in vitro studies. The present review examines the question of the extent to which the increase in bile acids in plasma could be responsible for the hyperdynamic circulatory disturbance of liver cirrhosis and whether modulation of the bile acid pool, for example, via administration of ursodeoxycholic acid (UDCA) or via modulation of the dysbiosis present in liver cirrhosis could influence the hemodynamic disorder of liver cirrhosis. According to our analysis, the evidence for this is limited. Long-term studies on this question are lacking.
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Affiliation(s)
- Tilman Sauerbruch
- Department of Internal Medicine I, University of Bonn, Bonn, Germany
| | - Martin Hennenberg
- Department of Urology I, University Hospital, LMU Munich, Munich, Germany
| | - Jonel Trebicka
- Translational Hepatology, Medical Department, University of Frankfurt, Frankfurt, Germany
| | - Ulrich Beuers
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, location AMC, Amsterdam, Netherlands
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Abstract
Bile acids (BAs) are a family of hydroxylated steroids secreted by the liver that aid in the breakdown and absorption of dietary fats. BAs also function as nutrient and inflammatory signaling molecules, acting through cognate receptors, to coordinate host metabolism. Commensal bacteria in the gastrointestinal tract are functional modifiers of the BA pool, affecting composition and abundance. Deconjugation of host BAs creates a molecular network that inextricably links gut microtia with their host. In this review we highlight the roles of BAs in mediating this mutualistic relationship with a focus on those events that impact host physiology and metabolism.
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Affiliation(s)
- James C Poland
- Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee
| | - C Robb Flynn
- Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee
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Yin H, Chen W, Dong L, Zhou S, Gong F, He X. Biliary diversion increases resting energy expenditure leading to decreased blood glucose level in mice with type 2 diabetes. J Diabetes Investig 2021; 12:931-939. [PMID: 33421302 PMCID: PMC8169353 DOI: 10.1111/jdi.13499] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2020] [Revised: 12/19/2020] [Accepted: 01/05/2021] [Indexed: 11/28/2022] Open
Abstract
AIMS/INTRODUCTION Type 2 diabetes mellitus is a group of metabolism abnormalities in carbohydrates and energy. Our aim was to investigate resting energy expenditure (REE) and blood glucose changes after biliary diversion in mice with diabetes. MATERIALS AND METHODS Male mice with diabetes were randomly divided into biliary diversion and sham groups. REE was detected by indirect calorimetry, the levels of fasting blood glucose, total bile acids and triiodothyronine were analyzed. After mice were killed, the weight amount of brown adipose tissue (BAT) and gastrocnemius was measured, and the expression level of G protein-coupled bile acid receptor and type 2 iodothyronine deiodinase in BAT and gastrocnemius were examined. RESULTS The two groups of mice were pair-fed, the bodyweights (P < 0.001) and the fasting blood glucose level (P < 0.001) in the biliary diversion group significantly decreased 24 weeks after surgery. The intraperitoneal glucose tolerance test (P = 0.035) and oral glucose tolerance test (P = 0.027) showed improvement in glucose tolerance after surgery. The REE level significantly increased 24 weeks after surgery (P = 0.005), the levels of total bile acids (P = 0.014) and triiodothyronine (P < 0.001) increased at the 24th postoperative week. The weight ratio of BAT (P = 0.038) and gastrocnemius (P = 0.026) in the biliary diversion group were higher than that in the sham group. The expression of G protein-coupled bile acid receptor in BAT (P < 0.001) and gastrocnemius (P = 0.003) were upregulated after surgery, and the type 2 iodothyronine deiodinase expression also increased in BAT (P = 0.015) and gastrocnemius (P = 0.015). CONCLUSIONS The REE level increased and the glucose metabolism improved in mice with diabetes after biliary diversion.
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Affiliation(s)
- Haixin Yin
- Department of General SurgeryPeking Union Medical College HospitalChinese Academy of Medical SciencesBeijingChina
| | - Weijie Chen
- Department of General SurgeryPeking Union Medical College HospitalChinese Academy of Medical SciencesBeijingChina
| | - Liangbo Dong
- Department of General SurgeryPeking Union Medical College HospitalChinese Academy of Medical SciencesBeijingChina
| | - Shengnan Zhou
- Department of General SurgeryPeking Union Medical College HospitalChinese Academy of Medical SciencesBeijingChina
| | - Fengying Gong
- Key Laboratory of Endocrinology of the Ministry of HealthDepartment of EndocrinologyPeking Union Medical College HospitalChinese Academy of Medical SciencesBeijingChina
| | - Xiaodong He
- Department of General SurgeryPeking Union Medical College HospitalChinese Academy of Medical SciencesBeijingChina
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Pregnancy and lactation after Roux-en-Y gastric bypass worsen nonalcoholic fatty liver disease in obese rats and lead to differential programming of hepatic de novo lipogenesis in offspring. J Dev Orig Health Dis 2021; 13:263-273. [PMID: 33998431 DOI: 10.1017/s2040174421000271] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Maternal obesity increases the risk of nonalcoholic fatty liver disease (NAFLD) in offspring. The Roux-en-Y gastric bypass (RYBG) is effective for achieving weight loss and ameliorates NAFLD. To determine whether these benefits are maintained after pregnancy and/or lactation, and whether they modulate hepatic morphofunction in the next generation, we evaluated hepatic lipid metabolism in Western diet (WD)-obese female rats that underwent RYGB and in their F1 offspring at adulthood. Female Wistar rats consumed a WD from 21 to 130 days of age, before being submitted to RYGB (WD-RYGB-F0) or SHAM (WD-SHAM-F0) operations. After 5 weeks, these females were mated with control male breeders, and the male and female F1 offspring were identified as WD-RYGB-F1 and WD-SHAM-F1. WD-RYGB-F0 dams exhibited lower serum lipids levels, but severe hepatic steatosis and pathological features of advanced liver injury. The hepatic proteins involved in lipogenesis were reduced in WD-RYGB-F0, as were the genes related to β-oxidation and bile acids (BAs). Although the female and male WD-RYGB-F1 groups did not exhibit hepatic steatosis, the livers of female WD-RYGB-F1 demonstrated higher amounts of lipogenic genes and proteins, while male WD-RYGB-F1 presented a similar downregulation of lipogenic factors to that seen in WD-RYGB-F0 dams. In contrast, maternal and offspring groups of both sexes displayed reductions in the expressions of genes involved in BAs physiology and gluconeogenesis. As such, RYGB aggravates NAFLD after pregnancy and lactation and induces a gender-dependent differential expression of the hepatic lipogenesis pathway in offspring, indicating that female WD-RYGB-F1 may be an increased risk of developing NAFLD.
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Ueno T, Tanaka N, Imoto H, Maekawa M, Kohyama A, Watanabe K, Motoi F, Kamei T, Unno M, Naitoh T. Mechanism of Bile Acid Reabsorption in the Biliopancreatic Limb After Duodenal-Jejunal Bypass in Rats. Obes Surg 2021; 30:2528-2537. [PMID: 32291708 DOI: 10.1007/s11695-020-04506-3] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Bile acids (BAs) are important in the metabolic effects of bariatric surgery. Most BAs are reabsorbed in the ileum and recycled back to the liver. We have reported that this enterohepatic circulation was shortened by duodenal-jejunal bypass (DJB), and the biliopancreatic (BP)-limb plays an important role in reabsorption of BAs. However, the mechanism of BA reabsorption in BP-limb remains uncertain. We aimed to investigate the mechanisms of BA reabsorption after DJB, especially focusing on carrier-mediated transport of BAs and the impact of the presence or absence of lipids on BA reabsorption. METHODS Otsuka-Long-Evans-Tokushima fatty rats or Sprague-Dawley rats were assigned to a control group and DJB group. BA levels in the divided small intestine were quantified with liquid chromatography-mass spectrometry. Labeled BA was injected and perfused with BA transporter inhibitors or mixture of lipids in the isolated BP-limb, and bile was sampled and analyzed. RESULTS Conjugated BA levels in the BP-limb were significantly higher than that of the control group. BA absorption tended to decrease by the apical sodium-dependent BA transporter inhibitor and was significantly decreased by the organic anion-transporting peptide (OATP) inhibitor. BA absorption tended to increase in the absence of lipid solutions compared with that in the presence of lipid solutions. CONCLUSION We attributed the increased BA reabsorption in the BP-limb to lack of food in the BP-limb, which contains concentrated BAs and no lipids. OATP played an important role in BA reabsorption in the BP-limb. Therefore, BAs would be reabsorbed in different manners after DJB.
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Affiliation(s)
- Tomotaka Ueno
- Department of Surgery, Tohoku University Graduate School of Medicine, 1-1, Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan
| | - Naoki Tanaka
- Department of Surgery, Tohoku University Graduate School of Medicine, 1-1, Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan.
| | - Hirofumi Imoto
- Department of Surgery, Tohoku University Graduate School of Medicine, 1-1, Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan
| | - Masamitsu Maekawa
- Department of Pharmaceutical Sciences, Tohoku University Hospital, 1-1, Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan
| | - Atsushi Kohyama
- Department of Surgery, Tohoku University Graduate School of Medicine, 1-1, Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan
| | - Kazuhiro Watanabe
- Department of Surgery, Tohoku University Graduate School of Medicine, 1-1, Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan
| | - Fuyuhiko Motoi
- Department of Surgery, Tohoku University Graduate School of Medicine, 1-1, Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan
| | - Takashi Kamei
- Department of Surgery, Tohoku University Graduate School of Medicine, 1-1, Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan
| | - Michiaki Unno
- Department of Surgery, Tohoku University Graduate School of Medicine, 1-1, Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan
| | - Takeshi Naitoh
- Department of Surgery, Tohoku University Graduate School of Medicine, 1-1, Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan
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Abstract
PURPOSES Biliopancreatic diversion could improve type 2 diabetes mellitus. Our aim was to investigate the effects of biliary jejunostomy on the improvement of glucose. MATERIALS AND METHODS Twenty-seven type 2 diabetes patients underwent biliary jejunostomy between January 2013 and January 2018 in our hospital and were followed up. Demographic data, operation details, body weight, food intake, effects on diabetes control, and biomedical parameters were collected and analyzed. RESULTS As defined previously, 3 of 27 diabetes patients were "under control," 8 patients were "in remission," and 12 patients were "improved." The fasting glucose decreased from 9.7 ± 2.1 mmol/L before surgery to 7.9 ± 1.8 mmol/L 12 months after surgery (P = 0.001). The level of hemoglobin A1c in these patients was 9.1 ± 2.3% before surgery, and it decreased to 7.2 ± 1.3% 12 months after surgery (P < 0.001). There was no significant difference in the body weight index (P = 0.78) or food intake (P = 0.18) between the time prior to surgery and 12 months afterward. The average level of total bile acids increased significantly after surgery, from 6.7 ± 2.2 μmol/L before surgery to 8.6 ± 2.9 μmol/L 12 months after surgery (P < 0.001). CONCLUSIONS Fasting glucose in type 2 diabetes patients was improved after biliary jejunostomy. Increasing bile acids levels might play an important role in the remission of type 2 diabetes.
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Albaugh VL, Kindel TL, Nissen SE, Aminian A. Cardiovascular Risk Reduction Following Metabolic and Bariatric Surgery. Surg Clin North Am 2021; 101:269-294. [PMID: 33743969 DOI: 10.1016/j.suc.2020.12.012] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Cardiovascular disease (CVD) remains a leading cause of morbidity and mortality in developed countries, with worsening pandemics of type 2 diabetes mellitus and obesity as major cardiovascular (CV) risk factors. Clinical trials of nonsurgical obesity treatments have not shown benefits in CVD, although recent diabetes trials have demonstrated major CV benefits. In many retrospective and prospective cohort studies, however, metabolic (bariatric) surgery is associated with substantial and reproducible CVD benefits. Despite a lack of prospective, randomized clinical trials, data suggest metabolic surgery may be the most effective modality for CVD risk reduction, likely through weight loss and weight loss-independent mechanisms.
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Affiliation(s)
- Vance L Albaugh
- Department of General Surgery, Bariatric and Metabolic Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Tammy L Kindel
- Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Steven E Nissen
- Department of Cardiovascular Medicine, Heart & Vascular Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Ali Aminian
- Department of General Surgery, Bariatric and Metabolic Institute, Cleveland Clinic, 9500 Euclid Avenue, M61, Cleveland, OH 44195, USA.
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Xie C, Huang W, Young RL, Jones KL, Horowitz M, Rayner CK, Wu T. Role of Bile Acids in the Regulation of Food Intake, and Their Dysregulation in Metabolic Disease. Nutrients 2021; 13:nu13041104. [PMID: 33800566 PMCID: PMC8066182 DOI: 10.3390/nu13041104] [Citation(s) in RCA: 62] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 03/23/2021] [Accepted: 03/25/2021] [Indexed: 02/07/2023] Open
Abstract
Bile acids are cholesterol-derived metabolites with a well-established role in the digestion and absorption of dietary fat. More recently, the discovery of bile acids as natural ligands for the nuclear farnesoid X receptor (FXR) and membrane Takeda G-protein-coupled receptor 5 (TGR5), and the recognition of the effects of FXR and TGR5 signaling have led to a paradigm shift in knowledge regarding bile acid physiology and metabolic health. Bile acids are now recognized as signaling molecules that orchestrate blood glucose, lipid and energy metabolism. Changes in FXR and/or TGR5 signaling modulates the secretion of gastrointestinal hormones including glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), hepatic gluconeogenesis, glycogen synthesis, energy expenditure, and the composition of the gut microbiome. These effects may contribute to the metabolic benefits of bile acid sequestrants, metformin, and bariatric surgery. This review focuses on the role of bile acids in energy intake and body weight, particularly their effects on gastrointestinal hormone secretion, the changes in obesity and T2D, and their potential relevance to the management of metabolic disorders.
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Affiliation(s)
- Cong Xie
- Adelaide Medical School, Center of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide 5005, Australia; (C.X.); (W.H.); (R.L.Y.); (K.L.J.); (M.H.); (C.K.R.)
| | - Weikun Huang
- Adelaide Medical School, Center of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide 5005, Australia; (C.X.); (W.H.); (R.L.Y.); (K.L.J.); (M.H.); (C.K.R.)
- The ARC Center of Excellence for Nanoscale BioPhotonics, Institute for Photonics and Advanced Sensing, School of Physical Sciences, The University of Adelaide, Adelaide 5005, Australia
| | - Richard L. Young
- Adelaide Medical School, Center of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide 5005, Australia; (C.X.); (W.H.); (R.L.Y.); (K.L.J.); (M.H.); (C.K.R.)
- Nutrition, Diabetes & Gut Health, Lifelong Health Theme South Australian Health & Medical Research Institute, Adelaide 5005, Australia
| | - Karen L. Jones
- Adelaide Medical School, Center of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide 5005, Australia; (C.X.); (W.H.); (R.L.Y.); (K.L.J.); (M.H.); (C.K.R.)
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide 5005, Australia
| | - Michael Horowitz
- Adelaide Medical School, Center of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide 5005, Australia; (C.X.); (W.H.); (R.L.Y.); (K.L.J.); (M.H.); (C.K.R.)
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide 5005, Australia
| | - Christopher K. Rayner
- Adelaide Medical School, Center of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide 5005, Australia; (C.X.); (W.H.); (R.L.Y.); (K.L.J.); (M.H.); (C.K.R.)
- Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide 5005, Australia
| | - Tongzhi Wu
- Adelaide Medical School, Center of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide 5005, Australia; (C.X.); (W.H.); (R.L.Y.); (K.L.J.); (M.H.); (C.K.R.)
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide 5005, Australia
- Institute of Diabetes, School of Medicine, Southeast University, Nanjing 210009, China
- Correspondence:
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Steenackers N, Vanuytsel T, Augustijns P, Tack J, Mertens A, Lannoo M, Van der Schueren B, Matthys C. Adaptations in gastrointestinal physiology after sleeve gastrectomy and Roux-en-Y gastric bypass. Lancet Gastroenterol Hepatol 2021; 6:225-237. [PMID: 33581761 DOI: 10.1016/s2468-1253(20)30302-2] [Citation(s) in RCA: 64] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2020] [Revised: 07/27/2020] [Accepted: 07/29/2020] [Indexed: 01/19/2023]
Abstract
Linked to the growing obesity epidemic, demand for bariatric and metabolic surgery has increased, the most common procedures being sleeve gastrectomy and Roux-en-Y gastric bypass. Originally, bariatric procedures were described as purely restrictive, malabsorptive, or combined restrictive-malabsorptive procedures limiting food intake, nutrient absorption, or both. Nowadays, anatomical alterations are known to affect gastrointestinal physiology, which in turn affects the digestion and absorption of nutrients and drugs. Therefore, understanding gastrointestinal physiology is crucial to prevent postoperative nutritional deficiencies and to optimise postoperative drug therapy. Preclinical and clinical research indicates that sleeve gastrectomy accelerates liquid and solid gastric emptying and small intestinal transit, and increases bile acid serum levels, whereas its effects on gastrointestinal acidity, gastric and pancreatic secretions, surface area, and colonic transit remain largely unknown. Roux-en-Y gastric bypass diminishes gastric acid secretion, accelerates liquid gastric emptying, and increases bile acid serum levels, but its effects on intestinal pH, solid gastric emptying, intestinal transit time, gastric enzyme secretions, and surface area remain largely unknown. In this Review, we summarise current knowledge of the effects of these two procedures on gastrointestinal physiology and assess the knowledge gaps.
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Affiliation(s)
- Nele Steenackers
- Clinical and Experimental Endocrinology, KU Leuven, Leuven, Belgium
| | - Tim Vanuytsel
- Translational Research Center for Gastrointestinal Disorders, KU Leuven, Leuven, Belgium
| | - Patrick Augustijns
- Department of Chronic Diseases and Metabolism, and Drug Delivery and Disposition, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium
| | - Jan Tack
- Translational Research Center for Gastrointestinal Disorders, KU Leuven, Leuven, Belgium
| | - Ann Mertens
- Clinical and Experimental Endocrinology, KU Leuven, Leuven, Belgium
| | - Matthias Lannoo
- Clinical and Experimental Endocrinology, KU Leuven, Leuven, Belgium
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Zhao D, Cai C, Chen Q, Jin S, Yang B, Li N. High-Fat Diet Promotes DSS-Induced Ulcerative Colitis by Downregulated FXR Expression through the TGFB Pathway. BIOMED RESEARCH INTERNATIONAL 2020; 2020:3516128. [PMID: 33029504 PMCID: PMC7537687 DOI: 10.1155/2020/3516128] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Revised: 09/04/2020] [Accepted: 09/13/2020] [Indexed: 12/13/2022]
Abstract
Ulcerative colitis is one of the IBD which cause a chronic intestinal inflammation and dysfunctional of the mucosal barrier. For now, the incident of UC was steadily increased all over the world. It has become a novel independent risk factor of several severe diseases especially colon-rectal cancer. However, the etiology of UC was still obscure. Previous studies show that high-fat diet contributed to the pathogenesis of immune system dysregulation, and farnesoid X receptor (FXR) was also implicated in the pathogenesis of various inflammatory symptoms. Yet, their inner roles in the pathogenesis of UC have not been mentioned. In this study, we aim to investigate the role of FXR in UC. High-fat diet (HFD) promotes the progression of DSS-induced UC, shows an increasing secretion of bile acid in serum, and leads to a downregulation of FXR target genes (FXRα, Shp, and lbabp). Adding FXR agonist FexD rescues the phenotype induced by high-fat diet, whereas TGFBRI inhibitor SB431542 abrogates the restoration by FexD in DSS-induced UC mice. To further verify the relationship between the FXR and TGFB signaling pathway, we made a UC-HFD model in the Caco2 cell line. Results shows the same conclusion that FXR mitigate UC inflammation through a TGFB-dependent pathway. These results expand the role of FXR in ulcerative colitis and suggest that FXR activation may be considered a therapeutic strategy for UC.
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Affiliation(s)
- Di Zhao
- Department of Colorectal Disease, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Chenwen Cai
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Inflammatory Bowel Disease Research Center, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai, China
| | - Qiyi Chen
- Department of Colorectal Disease, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Shuang Jin
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Inflammatory Bowel Disease Research Center, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai, China
| | - Bo Yang
- Department of Colorectal Disease, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Ning Li
- Department of Colorectal Disease, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
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Albaugh VL. Comment on: Fecal metagenomics and metabolomics reveal gut microbial changes after bariatric surgery. Surg Obes Relat Dis 2020; 16:1782-1783. [PMID: 32962897 DOI: 10.1016/j.soard.2020.08.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2020] [Accepted: 08/16/2020] [Indexed: 11/17/2022]
Affiliation(s)
- Vance L Albaugh
- Bariatric & Metabolic Institute - Cleveland Clinic, Cleveland, Ohio
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50
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Gut microbial metabolites as multi-kingdom intermediates. Nat Rev Microbiol 2020; 19:77-94. [PMID: 32968241 DOI: 10.1038/s41579-020-0438-4] [Citation(s) in RCA: 718] [Impact Index Per Article: 143.6] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/12/2020] [Indexed: 02/07/2023]
Abstract
The gut microbiota contributes to host physiology through the production of a myriad of metabolites. These metabolites exert their effects within the host as signalling molecules and substrates for metabolic reactions. Although the study of host-microbiota interactions remains challenging due to the high degree of crosstalk both within and between kingdoms, metabolite-focused research has identified multiple actionable microbial targets that are relevant for host health. Metabolites, as the functional output of combined host and microorganism interactions, provide a snapshot in time of an extraordinarily complex multi-organism system. Although substantial work remains towards understanding host-microbiota interactions and the underlying mechanisms, we review the current state of knowledge for each of the major classes of microbial metabolites with emphasis on clinical and translational research implications. We provide an overview of methodologies available for measurement of microbial metabolites, and in addition to discussion of key challenges, we provide a potential framework for integration of discovery-based metabolite studies with mechanistic work. Finally, we highlight examples in the literature where this approach has led to substantial progress in understanding host-microbiota interactions.
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