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1
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Zeng X, Xing YH, Ma XM, Long Y, Jiang ZZ, Xu Y. Proteomic and metabolomic profiling reveals the underlying molecular mechanisms in modified alternate-day fasting-mediated protection against Diabetic kidney disease. PLoS One 2025; 20:e0319053. [PMID: 39964999 PMCID: PMC11835337 DOI: 10.1371/journal.pone.0319053] [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: 08/22/2024] [Accepted: 01/26/2025] [Indexed: 02/20/2025] Open
Abstract
BACKGROUND Diabetic kidney disease (DKD) is a leading cause of chronic kidney disease, and while lifestyle interventions like intermittent fasting have shown promise in treating diabetes, the impact of modified alternate-day fasting (MADF) on DKD is not well understood. This study aimed to explore MADF's effects on DKD in db/db mice, a model for the condition, and to investigate its underlying mechanisms. METHODS We implemented an MADF regimen in db/db mice on a high-fat diet, measuring blood glucose, body weight, and renal function at various times. After the intervention, we analyzed the proteome and metabolome of renal tissues. RESULTS MADF was found to reduce hyperglycemia and slow the pathological progression of DKD in the mice. Proteomic analysis identified 165 proteins that increased and 196 that decreased in the kidneys of db/db mice compared to controls. MADF intervention led to a decrease in 26 of the increased proteins and an increase in 18 of the decreased ones. Notably, many of these proteins, including cathepsin S (CTSS), were related to lysosomes, suggesting a role in renal protection. Metabolomic profiling revealed changes in metabolites associated with inflammation, such as prostaglandin A1, which was downregulated in db/db mice and upregulated with MADF. Western blotting, immunohistochemistry, and immunofluorescence staining confirmed the expression changes of CTSS observed in the proteomic data. Additionally, CTSS expression was found to increase in renal cells exposed to high glucose and palmitic acid. CONCLUSION MADF appears to mitigate the progression of DKD, with proteomic evidence pointing to lysosome-related proteins like CTSS as potential mediators of its renal protective effects. These findings indicate that MADF and the inhibition of CTSS could be considered as novel therapeutic strategies for DKD treatment.
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Affiliation(s)
- Xin Zeng
- Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China
| | - Yi-hang Xing
- Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China
| | - Xiu-mei Ma
- Sichuan Provincial Key Laboratory for Human Disease Gene Study and Department of Laboratory Medicine, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Yang Long
- Metabolic Vascular Disease Key Laboratory of Sichuan Province, Sichuan, People’s Republic of China
- Sichuan Clinical Research Center for Nephropathy, Luzhou, Sichuan, People’s Republic of China
| | - Zong-zhe Jiang
- Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China
- Metabolic Vascular Disease Key Laboratory of Sichuan Province, Sichuan, People’s Republic of China
- Sichuan Clinical Research Center for Nephropathy, Luzhou, Sichuan, People’s Republic of China
| | - Yong Xu
- Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China
- Metabolic Vascular Disease Key Laboratory of Sichuan Province, Sichuan, People’s Republic of China
- Sichuan Clinical Research Center for Nephropathy, Luzhou, Sichuan, People’s Republic of China
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Kim HJ, Song SH. Steps to understanding diabetes kidney disease: a focus on metabolomics. Korean J Intern Med 2024; 39:898-905. [PMID: 39434603 PMCID: PMC11569920 DOI: 10.3904/kjim.2024.111] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Revised: 05/20/2024] [Accepted: 06/04/2024] [Indexed: 10/23/2024] Open
Abstract
Diabetic nephropathy (DN), a leading cause of chronic kidney disease and end-stage kidney disease (ESKD), poses global health challenges given its increasing prevalence. DN increases the risk of mortality and cardiovascular events. Early identification and appropriate DN management are crucial. However, current diagnostic methods rely on general traditional markers, highlighting the need for DN-specific diagnostics. Metabolomics, the study of small molecules produced by metabolic activity, promises to identify specific biomarkers that distinguish DN from other kidney diseases, decode the underlying disease mechanisms, and predict the disease course. Profound changes in metabolic pathways are apparent in individuals with DN, alterations in the tricarboxylic acid cycle and amino acid and lipid metabolism, suggestive of mitochondrial dysfunction. Metabolomics aids prediction of chronic kidney disease progression; several metabolites serve as indicators of renal functional decline and the risk of ESKD. Integration of such information with other omics data will further enhance our understanding of DN, paving the way to personalized treatment. In summary, metabolomics and multi-omics offer valuable insights into DN and are promising diagnostic and prognostic tools.
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Affiliation(s)
- Hyo Jin Kim
- Department of Internal Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan,
Korea
- Department of Internal Medicine, Pusan National University School of Medicine, Yangsan,
Korea
| | - Sang Heon Song
- Department of Internal Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan,
Korea
- Department of Internal Medicine, Pusan National University School of Medicine, Yangsan,
Korea
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Sharma V, Khokhar M, Panigrahi P, Gadwal A, Setia P, Purohit P. Advancements, Challenges, and clinical implications of integration of metabolomics technologies in diabetic nephropathy. Clin Chim Acta 2024; 561:119842. [PMID: 38969086 DOI: 10.1016/j.cca.2024.119842] [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: 03/30/2024] [Revised: 06/25/2024] [Accepted: 06/29/2024] [Indexed: 07/07/2024]
Abstract
BACKGROUND Diabetic nephropathy (DN), a severe complication of diabetes, involves a range of renal abnormalities driven by metabolic derangements. Metabolomics, revealing dynamic metabolic shifts in diseases like DN and offering insights into personalized treatment strategies, emerges as a promising tool for improved diagnostics and therapies. METHODS We conducted an extensive literature review to examine how metabolomics contributes to the study of DN and the challenges associated with its implementation in clinical practice. We identified and assessed relevant studies that utilized metabolomics methods, including nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS) to assess their efficacy in diagnosing DN. RESULTS Metabolomics unveils key pathways in DN progression, highlighting glucose metabolism, dyslipidemia, and mitochondrial dysfunction. Biomarkers like glycated albumin and free fatty acids offer insights into DN nuances, guiding potential treatments. Metabolomics detects small-molecule metabolites, revealing disease-specific patterns for personalized care. CONCLUSION Metabolomics offers valuable insights into the molecular mechanisms underlying DN progression and holds promise for personalized medicine approaches. Further research in this field is warranted to elucidate additional metabolic pathways and identify novel biomarkers for early detection and targeted therapeutic interventions in DN.
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Affiliation(s)
- V Sharma
- Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan 342005, India
| | - M Khokhar
- Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan 342005, India
| | - P Panigrahi
- Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan 342005, India
| | - A Gadwal
- Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan 342005, India
| | - P Setia
- Department of Forensic Medicine and Toxicology, All India Institute of Medical Sciences, Jodhpur, Rajasthan 342005, India
| | - P Purohit
- Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan 342005, India.
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Zhang F, Shan S, Fu C, Guo S, Liu C, Wang S. Advanced Mass Spectrometry-Based Biomarker Identification for Metabolomics of Diabetes Mellitus and Its Complications. Molecules 2024; 29:2530. [PMID: 38893405 PMCID: PMC11173766 DOI: 10.3390/molecules29112530] [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: 02/08/2024] [Revised: 04/15/2024] [Accepted: 04/16/2024] [Indexed: 06/21/2024] Open
Abstract
Over the years, there has been notable progress in understanding the pathogenesis and treatment modalities of diabetes and its complications, including the application of metabolomics in the study of diabetes, capturing attention from researchers worldwide. Advanced mass spectrometry, including gas chromatography-tandem mass spectrometry (GC-MS/MS), liquid chromatography-tandem mass spectrometry (LC-MS/MS), and ultra-performance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-Q-TOF-MS), etc., has significantly broadened the spectrum of detectable metabolites, even at lower concentrations. Advanced mass spectrometry has emerged as a powerful tool in diabetes research, particularly in the context of metabolomics. By leveraging the precision and sensitivity of advanced mass spectrometry techniques, researchers have unlocked a wealth of information within the metabolome. This technology has enabled the identification and quantification of potential biomarkers associated with diabetes and its complications, providing new ideas and methods for clinical diagnostics and metabolic studies. Moreover, it offers a less invasive, or even non-invasive, means of tracking disease progression, evaluating treatment efficacy, and understanding the underlying metabolic alterations in diabetes. This paper summarizes advanced mass spectrometry for the application of metabolomics in diabetes mellitus, gestational diabetes mellitus, diabetic peripheral neuropathy, diabetic retinopathy, diabetic nephropathy, diabetic encephalopathy, diabetic cardiomyopathy, and diabetic foot ulcers and organizes some of the potential biomarkers of the different complications with the aim of providing ideas and methods for subsequent in-depth metabolic research and searching for new ways of treating the disease.
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Affiliation(s)
- Feixue Zhang
- Hubei Key Laboratory of Diabetes and Angiopathy, Medicine Research Institute, Medical College, Hubei University of Science and Technology, Xianning 437100, China; (F.Z.); (C.F.); (S.G.)
| | - Shan Shan
- College of Life Science, National R&D Center for Freshwater Fish Processing, Jiangxi Normal University, Nanchang 330022, China;
| | - Chenlu Fu
- Hubei Key Laboratory of Diabetes and Angiopathy, Medicine Research Institute, Medical College, Hubei University of Science and Technology, Xianning 437100, China; (F.Z.); (C.F.); (S.G.)
- School of Pharmacy, Medical College, Hubei University of Science and Technology, Xianning 437100, China
| | - Shuang Guo
- Hubei Key Laboratory of Diabetes and Angiopathy, Medicine Research Institute, Medical College, Hubei University of Science and Technology, Xianning 437100, China; (F.Z.); (C.F.); (S.G.)
| | - Chao Liu
- Hubei Key Laboratory of Diabetes and Angiopathy, Medicine Research Institute, Medical College, Hubei University of Science and Technology, Xianning 437100, China; (F.Z.); (C.F.); (S.G.)
| | - Shuanglong Wang
- Jiangxi Key Laboratory for Mass Spectrometry and Instrumentation, East China University of Technology, Nanchang 330013, China
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Han YZ, Du BX, Zhu XY, Wang YZY, Zheng HJ, Liu WJ. Lipid metabolism disorder in diabetic kidney disease. Front Endocrinol (Lausanne) 2024; 15:1336402. [PMID: 38742197 PMCID: PMC11089115 DOI: 10.3389/fendo.2024.1336402] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2023] [Accepted: 04/09/2024] [Indexed: 05/16/2024] Open
Abstract
Diabetic kidney disease (DKD), a significant complication associated with diabetes mellitus, presents limited treatment options. The progression of DKD is marked by substantial lipid disturbances, including alterations in triglycerides, cholesterol, sphingolipids, phospholipids, lipid droplets, and bile acids (BAs). Altered lipid metabolism serves as a crucial pathogenic mechanism in DKD, potentially intertwined with cellular ferroptosis, lipophagy, lipid metabolism reprogramming, and immune modulation of gut microbiota (thus impacting the liver-kidney axis). The elucidation of these mechanisms opens new potential therapeutic pathways for DKD management. This research explores the link between lipid metabolism disruptions and DKD onset.
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Affiliation(s)
- Yi-Zhen Han
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Bo-Xuan Du
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Xing-Yu Zhu
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Yang-Zhi-Yuan Wang
- School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, China
| | - Hui-Juan Zheng
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Wei-Jing Liu
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
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Liu W, Zhu M, Liu J, Su S, Zeng X, Fu F, Lu Y, Rao Z, Chen Y. Comparison of the effects of monounsaturated fatty acids and polyunsaturated fatty acids on the lipotoxicity of islets. Front Endocrinol (Lausanne) 2024; 15:1368853. [PMID: 38501107 PMCID: PMC10945794 DOI: 10.3389/fendo.2024.1368853] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2024] [Accepted: 02/12/2024] [Indexed: 03/20/2024] Open
Abstract
Background Monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs) have been reported to combat saturated fatty acid (SFA)-induced cellular damage, however, their clinical effects on patients with metabolic diseases such as diabetes and hyperlipidemia are still controversial. Since comparative studies of the effects of these two types of unsaturated fatty acids (UFAs) are still limited. In this study, we aimed to compare the protective effects of various UFAs on pancreatic islets under the stress of SFA-induced metabolic disorder and lipotoxicity. Methods Rat insulinoma cell line INS-1E were treated with palmitic acid (PA) with or without UFAs including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA), and oleic acid (OA) to determine cell viability, apoptosis, endoplasmic reticulum (ER) stress, and inflammatory. In vivo, male C57BL/6 mice were fed a 60% high-fat diet (HFD) for 12 w. Then the lard in HFD was partially replaced with fish oil (FO) and olive oil (OO) at low or high proportions of energy (5% or 20%) to observe the ameliorative effects of the UFA supplement. Results All UFAs significantly improved PA-induced cell viability impairment in INS-1E cells, and their alleviation on PA induced apoptosis, ER stress and inflammation were confirmed. Particularly, OA had better effects than EPA, DHA, and AA on attenuating cellular ER stress. In vivo, the diets with a low proportion of UFAs (5% of energy) had limited effects on HFD induced metabolic disorder, except for a slight improved intraperitoneal glucose tolerance in obese mice. However, when fed diets containing a high proportion of UFAs (20% of energy), both the FO and OO groups exhibited substantially improved glucose and lipid metabolism, such as decrease in total cholesterol (TC), low-density lipoprotein (LDL), fasting blood glucose (FBG), and fasting blood insulin (FBI)) and improvement of insulin sensitivity evidenced by intraperitoneal glucose tolerance test (IPGTT) and intraperitoneal insulin tolerance test (IPITT). Unexpectedly, FO resulted in abnormal elevation of the liver function index aspartate aminotransferase (AST) in serum. Pathologically, OO attenuated HFD-induced compensatory hyperplasia of pancreatic islets, while this effect was not obvious in the FO group. Conclusions Both MUFAs and PUFAs can effectively protect islet β cells from SFA-induced cellular lipotoxicity. In particular, both OA in vitro and OO in vivo showed superior activities on protecting islets function and enhance insulin sensitivity, suggesting that MUFAs might have greater potential for nutritional intervention on diabetes.
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Affiliation(s)
- Wen Liu
- Department of Clinical Nutrition and Key Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China
| | - Min Zhu
- Department of Clinical Nutrition and Key Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China
| | - Jingyi Liu
- Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
| | - Shan Su
- Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
| | - Xin Zeng
- Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
| | - Fudong Fu
- Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
| | - Yanrong Lu
- Department of Clinical Nutrition and Key Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China
| | - Zhiyong Rao
- Department of Clinical Nutrition, West China Hospital, Sichuan University, Chengdu, China
| | - Younan Chen
- Department of Clinical Nutrition and Key Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China
- Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
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Yazıcı D, Demir SÇ, Sezer H. Insulin Resistance, Obesity, and Lipotoxicity. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2024; 1460:391-430. [PMID: 39287860 DOI: 10.1007/978-3-031-63657-8_14] [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: 09/19/2024]
Abstract
Lipotoxicity, originally used to describe the destructive effects of excess fat accumulation on glucose metabolism, causes functional impairments in several metabolic pathways, both in adipose tissue and peripheral organs, like liver, heart, pancreas, and muscle. Ectopic lipid accumulation in the kidneys, liver, and heart has important clinical counterparts like diabetic nephropathy in type 2 diabetes mellitus, obesity-related glomerulopathy, nonalcoholic fatty liver disease, and cardiomyopathy. Insulin resistance due to lipotoxicity indirectly lead to reproductive system disorders, like polycystic ovary syndrome. Lipotoxicity has roles in insulin resistance and pancreatic beta-cell dysfunction. Increased circulating levels of lipids and the metabolic alterations in fatty acid utilization and intracellular signaling have been related to insulin resistance in muscle and liver. Different pathways, like novel protein kinase c pathways and the JNK-1 pathway, are involved as the mechanisms of how lipotoxicity leads to insulin resistance in nonadipose tissue organs, such as liver and muscle. Mitochondrial dysfunction plays a role in the pathogenesis of insulin resistance. Endoplasmic reticulum stress, through mainly increased oxidative stress, also plays an important role in the etiology of insulin resistance, especially seen in non-alcoholic fatty liver disease. Visceral adiposity and insulin resistance both increase the cardiometabolic risk, and lipotoxicity seems to play a crucial role in the pathophysiology of these associations.
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Affiliation(s)
- Dilek Yazıcı
- Koç University Medical School, Section of Endocrinology and Metabolism, Koç University Hospital, Topkapi, Istanbul, Turkey.
| | - Selin Çakmak Demir
- Koç University Medical School, Section of Endocrinology and Metabolism, Koç University Hospital, Topkapi, Istanbul, Turkey
| | - Havva Sezer
- Koç University Medical School, Section of Endocrinology and Metabolism, Koç University Hospital, Topkapi, Istanbul, Turkey
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Liu P, Chen Q, Zhang L, Ren C, Shi B, Zhang J, Wang S, Chen Z, Wang Q, Xie H, Huang Q, Tang H. Rapid quantification of 50 fatty acids in small amounts of biological samples for population molecular phenotyping. BIOPHYSICS REPORTS 2023; 9:299-308. [PMID: 38524698 PMCID: PMC10960574 DOI: 10.52601/bpr.2023.230042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2023] [Accepted: 12/15/2023] [Indexed: 03/26/2024] Open
Abstract
Efficient quantification of fatty-acid (FA) composition (fatty-acidome) in biological samples is crucial for understanding physiology and pathophysiology in large population cohorts. Here, we report a rapid GC-FID/MS method for simultaneous quantification of all FAs in numerous biological matrices. Within eight minutes, this method enabled simultaneous quantification of 50 FAs as fatty-acid methyl esters (FAMEs) in femtomole levels following the efficient transformation of FAs in all lipids including FFAs, cholesterol-esters, glycerides, phospholipids and sphingolipids. The method showed satisfactory inter-day and intra-day precision, stability and linearity (R2 > 0.994) within a concentration range of 2-3 orders of magnitude. FAs were then quantified in typical multiple biological matrices including human biofluids (urine, plasma) and cells, animal intestinal content and tissue samples. We also established a quantitative structure-retention relationship (QSRR) for analytes to accurately predict their retention time and aid their reliable identification. We further developed a novel no-additive retention index (NARI) with endogenous FAMEs reducing inter-batch variations to 15 seconds; such NARI performed better than the alkanes-based classical RI, making meta-analysis possible for data obtained from different batches and platforms. Collectively, this provides an inexpensive high-throughput analytical system for quantitative phenotyping of all FAs in 8-minutes multiple biological matrices in large cohort studies of pathophysiological effects.
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Affiliation(s)
- Pinghui Liu
- State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Zhangjiang Fudan International Innovation Center, Metabonomics and Systems Biology Laboratory at Shanghai International Centre for Molecular Phenomics, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Qinsheng Chen
- State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Zhangjiang Fudan International Innovation Center, Metabonomics and Systems Biology Laboratory at Shanghai International Centre for Molecular Phenomics, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Lianglong Zhang
- State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Zhangjiang Fudan International Innovation Center, Metabonomics and Systems Biology Laboratory at Shanghai International Centre for Molecular Phenomics, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Chengcheng Ren
- State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Zhangjiang Fudan International Innovation Center, Metabonomics and Systems Biology Laboratory at Shanghai International Centre for Molecular Phenomics, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Biru Shi
- State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Zhangjiang Fudan International Innovation Center, Metabonomics and Systems Biology Laboratory at Shanghai International Centre for Molecular Phenomics, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Jingxian Zhang
- State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Zhangjiang Fudan International Innovation Center, Metabonomics and Systems Biology Laboratory at Shanghai International Centre for Molecular Phenomics, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Shuaiyao Wang
- State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Zhangjiang Fudan International Innovation Center, Metabonomics and Systems Biology Laboratory at Shanghai International Centre for Molecular Phenomics, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Ziliang Chen
- Wuhan Laboratory for Shanghai Metabolome Institute (SMI) Ltd, Wuhan 430000, China
| | - Qi Wang
- State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Zhangjiang Fudan International Innovation Center, Metabonomics and Systems Biology Laboratory at Shanghai International Centre for Molecular Phenomics, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Hui Xie
- State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Zhangjiang Fudan International Innovation Center, Metabonomics and Systems Biology Laboratory at Shanghai International Centre for Molecular Phenomics, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Qingxia Huang
- State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Zhangjiang Fudan International Innovation Center, Metabonomics and Systems Biology Laboratory at Shanghai International Centre for Molecular Phenomics, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Huiru Tang
- State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Zhangjiang Fudan International Innovation Center, Metabonomics and Systems Biology Laboratory at Shanghai International Centre for Molecular Phenomics, Zhongshan Hospital, Fudan University, Shanghai 200032, China
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9
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Missio D, Leivas FG, Cibin F, Emanuelli T, Somacal S, Buss V, Gasperin B, Oliveira DED, Gonçalves PBD, Ferreira R. Vitamin E reduces the reactive oxygen species production in dominant follicle during the negative energy balance in cattle. Reprod Domest Anim 2023; 58:1662-1671. [PMID: 37743826 DOI: 10.1111/rda.14481] [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: 08/10/2023] [Revised: 09/07/2023] [Accepted: 09/14/2023] [Indexed: 09/26/2023]
Abstract
In the postpartum period, there is an increase in non-esterified fatty acids (NEFA) in both serum and follicular fluid (FF) of cattle. The increase in fatty acid concentration results in increased production of reactive oxygen species (ROS) that can compromise bovine fertility. The objectives of this study were to characterize the lipid profile found in the FF of cows experiencing induced negative energy balance (NEB) and to evaluate the effect of α-tocopherol in the prevention of oxidative stress in the serum and FF of cows. Twenty-nine beef cows were divided into groups: (1) control; (2) Fasting for 24 days; and (3) Fasting + VitE. Between D0 and D4 blood samples were taken to assess concentrations of NEFA, ROS production, total antioxidant capacity (FRAP), lipid peroxidation, and α-tocopherol (vitamin E). On D4, follicular aspiration was performed for analysis of FF from the dominant follicle. Our results demonstrate that fasting was effective in causing increased fat mobilization in animals. The increase in serum concentration of C18:1c9 was reflected in the FF of fasting cows. Serum α-tocopherol concentration was higher in the control and Fasting + VitE groups compared to the Fasting group. In FF, there was an increase of α-tocopherol in the Fasting + VitE group in comparison to Fasting cows. There was an increase in ROS production in the serum of fasting cows. ROS production in FF was higher in the Fasting compared to the Fasting + VitE group. Vitamin E has beneficial effects in reducing ROS production in the dominant follicle of cows in NEB.
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Affiliation(s)
- Daniele Missio
- Laboratory of Biotechnology of Reproduction, Federal University of Santa Maria, Santa Maria, Brazil
| | - Fabio Gallas Leivas
- Laboratory of Biotechnology of Reproduction, BIOTECH, Federal University of Pampa, Uruguaiana, Brazil
| | - Francielli Cibin
- Laboratory of Biotechnology of Reproduction, BIOTECH, Federal University of Pampa, Uruguaiana, Brazil
| | - Tatiana Emanuelli
- Department of Alimentary Technology and Science, Federal University of Santa Maria, Santa Maria, Brazil
| | - Sabrina Somacal
- Department of Alimentary Technology and Science, Federal University of Santa Maria, Santa Maria, Brazil
| | - Vanessa Buss
- Laboratory of Biotechnology of Reproduction, BIOTECH, Federal University of Pampa, Uruguaiana, Brazil
| | - Bernardo Gasperin
- Department of Animal Pathology, Federal University of Pelotas, Capão do Leão, Brazil
| | | | | | - Rogério Ferreira
- Department of Animal Science, Santa Catarina State University, Chapecó, Brazil
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10
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Qi L, Ye Z, Lin H. Identification of Differential Metabolites Between
Type 2 Diabetes and Postchronic Pancreatitis Diabetes (Type 3c) Based on an Untargeted Metabolomics Approach. Lab Med 2023; 54:562-573. [PMID: 36864551 DOI: 10.1093/labmed/lmad004] [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: 03/04/2023] Open
Abstract
OBJECTIVE A nontargeted metabolomics approach was established to characterize serum metabolic profile in type 3c diabetes mellitus (T3cDM) secondary to chronic pancreatitis and compare with T2DM. METHODS Forty patients were recruited for metabolite analysis based on liquid chromatography-mass spectrometry. Cluster heatmap and KEGG metabolic pathway enrichment analysis were used to analyze the specific and differential metabolites. The receiver operating characteristics (ROCs) were generated and correlation analysis with clinical data was conducted. RESULTS Metabolites including sphingosine, lipids, carnitine, bile acid, and hippuric acid were found to be different between T2DM and T3cDM, mainly enriched in bile acid biosynthesis, fatty acid biosynthesis, and sphingolipid metabolic pathways. The ROCs were generated with an area under the curve of 0.907 (95% confidence interval, 0.726-1) for the model with 15 metabolites. CONCLUSION T3cDM is characterized by increased sphingosine, carnitine, bile acid, and most lipids, providing novel biomarkers for clinical diagnosis and a future direction in research on pathophysiological mechanisms.
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Affiliation(s)
- Liang Qi
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Zheng Ye
- State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, China
| | - Hao Lin
- Department of Clinical Science and Research, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
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Zhou X, Zhang J, Sun Y, Shen J, Sun B, Ma Q. Glutamine Ameliorates Liver Steatosis via Regulation of Glycolipid Metabolism and Gut Microbiota in High-Fat Diet-Induced Obese Mice. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2023; 71:15656-15667. [PMID: 37847053 DOI: 10.1021/acs.jafc.3c05566] [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: 10/18/2023]
Abstract
Obesity and its associated conditions, such as nonalcoholic fatty liver disease (NAFLD), are risk factors for health. The aim of this study was to explore the effects of glutamine (Gln) on liver steatosis induced by a high-fat diet (HFD) and HEPG2 cells induced by oleic acid. Gln demonstrated a positive influence on hepatic homeostasis by suppressing acetyl CoA carboxylase (ACC) and fatty acid synthase (FAS) and promoting sirtuin 1 (SIRT1) expression while improving glucose metabolism by regulating serine/threonine protein kinase (AKT)/factor forkhead box O1 (FOXO1) signals in vivo and in vitro. Obese Gln-fed mice had higher colonic short-chain fatty acid (SCFA) contents and lower inflammation factor protein levels in the liver, HEPG2 cells, and jejunum. Gln-treated obese mice had an effective decrease in Firmicutes abundance. These findings indicate that Gln serves as a nutritional tool in managing obesity and related disorders.
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Affiliation(s)
- Xinbo Zhou
- College of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, China
| | - Junjie Zhang
- College of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, China
| | - Yutong Sun
- College of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, China
| | - Jian Shen
- College of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, China
| | - Bo Sun
- College of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, China
| | - Qingquan Ma
- College of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, China
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12
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Wang Y, Li T, Yang C, Wu Y, Liu Y, Yang X. Eurotium cristatum from Fu Brick Tea Promotes Adipose Thermogenesis by Boosting Colonic Akkermansia muciniphila in High-Fat-Fed Obese Mice. Foods 2023; 12:3716. [PMID: 37893609 PMCID: PMC10606327 DOI: 10.3390/foods12203716] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Revised: 09/23/2023] [Accepted: 10/07/2023] [Indexed: 10/29/2023] Open
Abstract
This study investigated the potential fat-thermogenic effects of Eurotium cristatum, and elucidated the underlying mechanisms. The 12-week administration of E. cristatum in HFD-fed obese mice reduced body weight and improved glucolipid metabolism disorders. The administration of E. cristatum also efficiently promoted thermogenesis by increasing the expression of UCP1 and PRDM16 in both interscapular brown adipose tissue (iBAT) and inguinal white adipose tissue (iWAT) of HFD-fed mice. Furthermore, E. cristatum shaped the gut microbiome by increasing the abundance of Parabacteroides and Akkermansia muciniphila, and also elevated the levels of cecal short-chain fatty acids, particularly propionate and acetate. Of note, A. muciniphila was highly negatively correlated with body weight gain (r = -0.801, p < 0.05) and the iWAT index (r = -0.977, p < 0.01), suggesting that A. muciniphila may play an important role in the thermogenic mobilization induced by E. cristatum. Continuous supplementation with A. muciniphila suppressed adipose accumulation, improved glucolipid metabolism, and enhanced the thermogenic activity of iWAT and iBAT. Collectively, our results propose that boosted A. muciniphila acts as a key microbe in tea-derived probiotic E. cristatum-mediated fat-thermogenic and anti-obesity effects.
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Affiliation(s)
| | | | | | | | | | - Xingbin Yang
- College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi’an 710119, China (T.L.)
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13
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Hammad SM, Lopes-Virella MF. Circulating Sphingolipids in Insulin Resistance, Diabetes and Associated Complications. Int J Mol Sci 2023; 24:14015. [PMID: 37762318 PMCID: PMC10531201 DOI: 10.3390/ijms241814015] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2023] [Revised: 09/05/2023] [Accepted: 09/06/2023] [Indexed: 09/29/2023] Open
Abstract
Sphingolipids play an important role in the development of diabetes, both type 1 and type 2 diabetes, as well as in the development of both micro- and macro-vascular complications. Several reviews have been published concerning the role of sphingolipids in diabetes but most of the emphasis has been on the possible mechanisms by which sphingolipids, mainly ceramides, contribute to the development of diabetes. Research on circulating levels of the different classes of sphingolipids in serum and in lipoproteins and their importance as biomarkers to predict not only the development of diabetes but also of its complications has only recently emerged and it is still in its infancy. This review summarizes the previously published literature concerning sphingolipid-mediated mechanisms involved in the development of diabetes and its complications, focusing on how circulating plasma sphingolipid levels and the relative content carried by the different lipoproteins may impact their role as possible biomarkers both in the development of diabetes and mainly in the development of diabetic complications. Further studies in this field may open new therapeutic avenues to prevent or arrest/reduce both the development of diabetes and progression of its complications.
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Affiliation(s)
- Samar M. Hammad
- Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29425, USA
| | - Maria F. Lopes-Virella
- Division of Endocrinology, Diabetes and Medical Genetics, Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA
- Ralph H. Johnson VA Medical Center, Charleston, SC 29425, USA
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14
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Alim A, Li T, Nisar T, Ali Z, Ren D, Liu Y, Yang X. Polyphenols and pectin enriched golden kiwifruit (Actinidia chinensis) alleviates high fructose-induced glucolipid disorders and hepatic oxidative damage in rats: in association with improvement of fatty acids metabolism. FOOD SCIENCE AND HUMAN WELLNESS 2023. [DOI: 10.1016/j.fshw.2023.02.039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/28/2023]
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15
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Serum Metabolites Characterization Produced by Cats CKD Affected, at the 1 and 2 Stages, before and after Renal Diet. Metabolites 2022; 13:metabo13010043. [PMID: 36676969 PMCID: PMC9863800 DOI: 10.3390/metabo13010043] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Revised: 12/20/2022] [Accepted: 12/20/2022] [Indexed: 12/29/2022] Open
Abstract
Utilizing metabolomics, a tool for measuring and characterizing low-molecular-weight substances (LMWs), to identify eventual changes in response to dietary intervention is novel in cats with chronic kidney disease (CKD), a condition characterized by retention of uremic solutes. This study aims to assess the serum metabolomic profile of cats in early stages of CKD and to compare the serum metabolomic of CKD cats after 60 days of a renal diet to evaluate the effect of dietary intervention on these metabolites. Twenty-five domestic cats were included in the study. Fifteen cats with CKD stages 1 (n = 6) and 2 (n = 9) according to the International Renal Interest Society (IRIS) were included in the renal groups, and a control group consisting of 10 cats was included. All animals were enrolled on a maintenance diet for 30 days before the experimental period. The metabolomics analysis was performed by gas chromatography-mass spectrometry (GC-MS). Partial least squares discriminant analysis (PLS-DA) was performed on Metaboanalyst 4.0 software. Forty-three metabolites were identified. Citric acid and monostearin were altered in the CKD2 group when compared to CKD1 and the control group at T0. A total of seven serum metabolites differed after 60 days of the renal diet: glycine, fructose, glutamic acid, arachidonic acid, stearic acid, creatinine, and urea. Changes were seen in the serum metabolomic profile after 60 days of the renal diet, and some of the metabolites that changed in response to the diet have beneficial effects on health. Overall, metabolomics markers have the potential to identify early stages of CKD, providing insights into the possible pathophysiologic processes that contribute to the development and progression of CKD.
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16
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Jung CY, Yoo TH. Novel biomarkers for diabetic kidney disease. Kidney Res Clin Pract 2022; 41:S46-S62. [DOI: 10.23876/j.krcp.22.084] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2022] [Accepted: 06/17/2022] [Indexed: 11/04/2022] Open
Abstract
Although diabetic kidney disease (DKD) remains one of the leading causes of reduced lifespan in patients with diabetes mellitus; its prevalence has failed to decline over the past 30 years. To identify those at high risk of developing DKD and disease progression at an early stage, extensive research has been ongoing in the search for prognostic and surrogate endpoint biomarkers for DKD. Although biomarkers are not used routinely in clinical practice or prospective clinical trials, many biomarkers have been developed to improve the early identification and prognostication of patients with DKD. Novel biomarkers that capture one specific mechanism of the DKD disease process have been developed, and studies have evaluated the prognostic value of assay-based biomarkers either in small sets or in combinations involving multiple biomarkers. More recently, several studies have assessed the prognostic value of omics- based biomarkers that include proteomics, metabolomics, and transcriptomics. This review will first describe the biomarkers used in current practice and their limitations, and then summarize the current status of novel biomarkers for DKD with respect to assay- based protein biomarkers, proteomics, metabolomics, and transcriptomics.
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17
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Chai J, Sun Z, Xu J. A Contemporary Insight of Metabolomics Approach for Type 1 Diabetes: Potential for Novel Diagnostic Targets. Diabetes Metab Syndr Obes 2022; 15:1605-1625. [PMID: 35642181 PMCID: PMC9148614 DOI: 10.2147/dmso.s357007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Accepted: 04/08/2022] [Indexed: 11/23/2022] Open
Abstract
High-throughput omics has been widely applied in metabolic disease, type 1 diabetes (T1D) was one of the most typical diseases. Effective prevention and early diagnosis are very important because of infancy and persistent characteristics of T1D. The occurrence and development of T1D is a chronic and continuous process, in which the production of autoantibodies (ie serum transformation) occupies the central position. Metabolomics can evaluate the metabolic characteristics of serum before seroconversion, the changes with age and T1D complications. And the addition of natural drug metabolomics is more conducive to the systematic and comprehensive diagnosis and treatment of T1D. This paper reviewed the metabolic changes and main pathogenesis from pre-diagnosis to treatment in T1D. The metabolic spectrum of significant abnormal energy and glucose-related metabolic pathway, down-regulation of lipid metabolism and up-regulation of some antioxidant pathways has appeared before seroconversion, indicating that the body has been in the dual state of disease progression and disease resistance before T1D onset. Some metabolites (such as methionine) are closely related to age, and the types of autoantibodies produced are age-specific. Some metabolites may jointly predict DN with eGFR, and metabolomics can further contribute to the pathogenesis based on the correlation between DN and DR. Many natural drug components have been proved to act on abnormal metabolic pathways of T1D and have a positive impact on some metabolic levels, which is very important for further finding therapeutic targets and developing new drugs with small side effects. Metabolomics can provide auxiliary value for the diagnosis of T1D and provide a new direction to reveal the pathogenesis of T1D and find new therapeutic targets. The development of T1D metabolomics shows that high-throughput research methods are expected to be introduced into clinical practice.
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Affiliation(s)
- Jiatong Chai
- Department of Laboratory Medicine, The First Hospital of Jilin University, Changchun, People’s Republic of China
| | - Zeyu Sun
- Department of Laboratory Medicine, The First Hospital of Jilin University, Changchun, People’s Republic of China
| | - Jiancheng Xu
- Department of Laboratory Medicine, The First Hospital of Jilin University, Changchun, People’s Republic of China
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18
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Pereira PR, Carrageta DF, Oliveira PF, Rodrigues A, Alves MG, Monteiro MP. Metabolomics as a tool for the early diagnosis and prognosis of diabetic kidney disease. Med Res Rev 2022; 42:1518-1544. [PMID: 35274315 DOI: 10.1002/med.21883] [Citation(s) in RCA: 47] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Revised: 01/26/2022] [Accepted: 02/22/2022] [Indexed: 01/21/2023]
Abstract
Diabetic kidney disease (DKD) is one of the most prevalent comorbidities of diabetes mellitus and the leading cause of the end-stage renal disease (ESRD). DKD results from chronic exposure to hyperglycemia, leading to progressive alterations in kidney structure and function. The early development of DKD is clinically silent and when albuminuria is detected the lesions are often at advanced stages, leading to rapid kidney function decline towards ESRD. DKD progression can be arrested or substantially delayed if detected and addressed at early stages. A major limitation of current methods is the absence of albuminuria in non-albuminuric phenotypes of diabetic nephropathy, which becomes increasingly prevalent and lacks focused therapy. Metabolomics is an ever-evolving omics technology that enables the study of metabolites, downstream products of every biochemical event that occurs in an organism. Metabolomics disclosures complex metabolic networks and provide knowledge of the very foundation of several physiological or pathophysiological processes, ultimately leading to the identification of diseases' unique metabolic signatures. In this sense, metabolomics is a promising tool not only for the diagnosis but also for the identification of pre-disease states which would confer a rapid and personalized clinical practice. Herein, the use of metabolomics as a tool to identify the DKD metabolic signature of tubule interstitial lesions to diagnose or predict the time-course of DKD will be discussed. In addition, the proficiency and limitations of the currently available high-throughput metabolomic techniques will be discussed.
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Affiliation(s)
- Pedro R Pereira
- Clinical and Experimental Endocrinology, UMIB - Unit for Multidisciplinary Research in Biomedicine, ICBAS, School of Medicine and Biomedical Sciences, University of Porto, Porto, Portugal.,ITR - Laboratory for Integrative and Translational Research in Population Health, Porto, Portugal.,Department of Nephrology, Centro Hospitalar de Trás-os-Montes e Alto Douro (CHTMAD, EPE), Vila Real, Portugal
| | - David F Carrageta
- Clinical and Experimental Endocrinology, UMIB - Unit for Multidisciplinary Research in Biomedicine, ICBAS, School of Medicine and Biomedical Sciences, University of Porto, Porto, Portugal.,ITR - Laboratory for Integrative and Translational Research in Population Health, Porto, Portugal
| | - Pedro F Oliveira
- Department of Chemistry, QOPNA & LAQV, University of Aveiro, Aveiro, Portugal
| | - Anabela Rodrigues
- Department of Nephrology and Department of Clinical Pathology, Santo António General Hospital (Hospital Center of Porto, EPE), Porto, Portugal.,Nephrology, Dialysis and Transplantation, UMIB - Unit for Multidisciplinary Research in Biomedicine, ICBAS - School of Medicine and Biomedical Sciences, University of Porto, Porto, Portugal
| | - Marco G Alves
- Clinical and Experimental Endocrinology, UMIB - Unit for Multidisciplinary Research in Biomedicine, ICBAS, School of Medicine and Biomedical Sciences, University of Porto, Porto, Portugal.,ITR - Laboratory for Integrative and Translational Research in Population Health, Porto, Portugal.,Biotechnology of Animal and Human Reproduction (TechnoSperm), Institute of Food and Agricultural Technology, University of Girona, Girona, Spain.,Department of Biology, Unit of Cell Biology, Faculty of Sciences, University of Girona, Girona, Spain
| | - Mariana P Monteiro
- Clinical and Experimental Endocrinology, UMIB - Unit for Multidisciplinary Research in Biomedicine, ICBAS, School of Medicine and Biomedical Sciences, University of Porto, Porto, Portugal.,ITR - Laboratory for Integrative and Translational Research in Population Health, Porto, Portugal
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19
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Jung CY, Yoo TH. Pathophysiologic Mechanisms and Potential Biomarkers in Diabetic Kidney Disease. Diabetes Metab J 2022; 46:181-197. [PMID: 35385633 PMCID: PMC8987689 DOI: 10.4093/dmj.2021.0329] [Citation(s) in RCA: 90] [Impact Index Per Article: 30.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Accepted: 01/14/2022] [Indexed: 12/15/2022] Open
Abstract
Although diabetic kidney disease (DKD) remains the leading cause of end-stage kidney disease eventually requiring chronic kidney replacement therapy, the prevalence of DKD has failed to decline over the past 30 years. In order to reduce disease prevalence, extensive research has been ongoing to improve prediction of DKD onset and progression. Although the most commonly used markers of DKD are albuminuria and estimated glomerular filtration rate, their limitations have encouraged researchers to search for novel biomarkers that could improve risk stratification. Considering that DKD is a complex disease process that involves several pathophysiologic mechanisms such as hyperglycemia induced inflammation, oxidative stress, tubular damage, eventually leading to kidney damage and fibrosis, many novel biomarkers that capture one specific mechanism of the disease have been developed. Moreover, the increasing use of high-throughput omic approaches to analyze biological samples that include proteomics, metabolomics, and transcriptomics has emerged as a strong tool in biomarker discovery. This review will first describe recent advances in the understanding of the pathophysiology of DKD, and second, describe the current clinical biomarkers for DKD, as well as the current status of multiple potential novel biomarkers with respect to protein biomarkers, proteomics, metabolomics, and transcriptomics.
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Affiliation(s)
- Chan-Young Jung
- Department of Internal Medicine and Institute of Kidney Disease Research, Yonsei University College of Medicine, Seoul, Korea
| | - Tae-Hyun Yoo
- Department of Internal Medicine and Institute of Kidney Disease Research, Yonsei University College of Medicine, Seoul, Korea
- Corresponding author: Tae-Hyun Yoo https://orcid.org/0000-0002-9183-4507 Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea E-mail:
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20
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Guo J, Zhang M, Wang H, Li N, Lu Z, Li L, Hui S, Xu H. Gut microbiota and short chain fatty acids partially mediate the beneficial effects of inulin on metabolic disorders in obese ob/ob mice. J Food Biochem 2022; 46:e14063. [PMID: 35128673 DOI: 10.1111/jfbc.14063] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Revised: 11/25/2021] [Accepted: 12/06/2021] [Indexed: 02/01/2023]
Abstract
Mounting evidence has linked both obesity and metabolic disorders with dysbiosis of the gut microbiota. Dietary inulin is conducive to modulating this dysbiosis, and represents a potential means to improve disorders of glucose and lipid metabolism. However, the mechanisms underlying these improvements are largely unclear. Obese ob/ob mice were fed a standard chow, a low fiber diet (LFD) or a high fiber diet (HFD) for 4 weeks, and the body weight, fecal short chain fatty acids (SCFAs) level, and plasma and liver lipid profiles were analyzed. Oral glucose tolerance testing, and gut microbiota sequencing were also conducted. Dietary inulin improved the dysbiosis of the gut microbiota, attenuated the decrease in phylum Bacteroidetes, repressed the increase of phylum Firmicutes, and led to an increase in the ratio of Firmicutes/Bacteroidetes. At the family level, inulin promoted the expansion of SCFAs-producing Ruminococcaceae and Lachnospiraceae bacteria, which increased the fecal SCFAs concentrations. At the genus level, inulin increased the levels of Bacteroides and Bifidobacteria. Furthermore, our results revealed that there was enhanced expression of angiopoietin-like protein 4 (ANGPTL4), which might be induced by the higher production of SCFAs, and this may underlie the improvements in the disorders of glucose and lipid metabolism seen in mice with added dietary inulin. In conclusion, inulin may ameliorate metabolic disorders by remodeling the gut microbiota and increasing the production of SCFAs, which might be mediated by the ANGPTL4-related signaling pathway. Interventions targeting the gut microbiota warrant further investigation as a novel therapy for metabolic diseases. PRACTICAL APPLICATIONS: Mounting evidence has linked both obesity and metabolic disorders with dysbiosis of the gut microbiota. Dietary inulin is conducive to modulating this dysbiosis, and represents a potential means to improve disorders of glucose and lipid metabolism. However, the mechanisms underlying these improvements are largely unclear. In the present study, we investigated the effects of dietary fiber (inulin) on metabolic homeostasis using ob/ob mice. The results of our study demonstrate that inulin-induced remodeling of the gut microbiota resulted in increased production of short chain fatty acids (SCFAs), leading to the enhanced expression of angiopoietin-like protein 4 (ANGPTL4), which improved the glucose and lipid metabolism. Our results suggest that the gut microbiota, SCFAs and ANGPTL4 pathway at least partially mediate the beneficial effects of inulin on metabolic disorders in ob/ob mice.
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Affiliation(s)
- Jing Guo
- Department of Clinical Nutrition, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Mengyuan Zhang
- Department of Clinical Nutrition, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - He Wang
- Department of Clinical Nutrition, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Na Li
- Department of Clinical Nutrition, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Zongliang Lu
- Department of Clinical Nutrition, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Long Li
- Department of Clinical Nutrition, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Suocheng Hui
- Research Department, The Rocket Force Characteristic Medical Center of Chinese People's Liberation Army, Beijing, China
| | - Hongxia Xu
- Department of Clinical Nutrition, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
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21
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Liu Y, Li Y, Shen H, Li Y, Xu Y, Zhou M, Xia X, Shi B. Association between the metabolic profile of serum fatty acids and diabetic nephropathy: a study conducted in northeastern China. Ther Adv Endocrinol Metab 2022; 13:20420188221118750. [PMID: 36157308 PMCID: PMC9490461 DOI: 10.1177/20420188221118750] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Accepted: 07/21/2022] [Indexed: 11/24/2022] Open
Abstract
BACKGROUND AND PURPOSE With the progressive increase in the prevalence of type 2 diabetes mellitus (T2DM), diabetic nephropathy (DN) - one of the most common chronic microvascular complications - has evolved into a significant cause of death worldwide among end-stage renal disease patients. Academic researchers have for decades focused on the development of DN and recently found that free fatty acids (FFAs) constituted an independent risk factor for vascular complications in T2DM patients. It is therefore critical to determine whether the metabolic profile of FFAs is related to DN. METHODS This study comprised 611 research subjects in Dalian, a city in northeast China: 52 DN patients, 115 T2DM patients, and 444 healthy controls. We determined 15 forms of serum FFAs, including arachidonic acid (AA, C20:4), docosahexaenoic acid (DHA, C22:6), erucic acid (C22:1), nervonic acid (NA, C24:1), estimated total omega-3s, total omega-6s, the omega-3/omega-6 ratio, and total FFA content by liquid chromatography-mass spectrometry (LC-MS). RESULTS The levels of NA (mean = 45.27, range = 0.84-76.57) and DHA (mean = 324.58, range = 205.38-450.03) in DN patients were slightly lower than those in T2DM patients or healthy controls. The serum omega-3 polyunsaturated fatty acid (PUFA) DHA (C22:6) was significantly negatively correlated with microalbuminuria (MAU), the albumin/creatinine ratio (ACR), body mass index (BMI), fasting plasma glucose (FPG), and glycosylated hemoglobin (HbA1c). The serum monounsaturated fatty acid (MUFA) NA (C24:1) was significantly negatively correlated with BMI, FPG, and HbA1c. After adjustment of variables, multiple logistic regression analysis revealed significant odds ratios (ORs) [with confidence intervals (CIs)] for DHA (0.991, 0.985-0.997; p = 0.002) and NA (0.978, 0.958-0.999; p = 0.037). CONCLUSION In this study, we ascertained that the contents of NA and DHA in patients with DN were relatively low, and that DHA was negatively correlated with MAU and the ACR. However, large-scale, population-based studies focusing on the role of NA and DHA in the pathogenesis of DN are still required in the future.
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Affiliation(s)
- Yazhuo Liu
- Department of Endocrinology, The First Affiliated Hospital, Xi’an Jiaotong University, Xi’an, China
| | - Yingying Li
- Department of Clinical Nutrition and Metabolism, Dalian University Affiliated Zhongshan Hospital, Dalian, China
| | - Hui Shen
- Department of Clinical Nutrition and Metabolism, Dalian University Affiliated Zhongshan Hospital, Dalian, China
| | - Yike Li
- Department of Clinical Nutrition and Metabolism, Dalian University Affiliated Zhongshan Hospital, Dalian, China
| | - Yanbing Xu
- Department of Clinical Nutrition and Metabolism, Dalian University Affiliated Zhongshan Hospital, Dalian, China
| | - Mi Zhou
- Department of Ophthalmology, Penn State Hershey Medical Center, Hershey, PA, USA
| | - Xinghai Xia
- Department of Ophthalmology, Penn State Hershey Medical Center, Hershey, PA, USA
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22
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Hammad SM, Hunt KJ, Baker NL, Klein RL, Lopes-Virella MF. Diabetes and kidney dysfunction markedly alter the content of sphingolipids carried by circulating lipoproteins. J Clin Lipidol 2022; 16:173-183. [DOI: 10.1016/j.jacl.2021.12.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Revised: 11/18/2021] [Accepted: 12/28/2021] [Indexed: 10/19/2022]
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23
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Wang Y, Zhao A, Du H, Liu Y, Qi B, Yang X. Theabrownin from Fu Brick Tea Exhibits the Thermogenic Function of Adipocytes in High-Fat-Diet-Induced Obesity. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2021; 69:11900-11911. [PMID: 34581185 DOI: 10.1021/acs.jafc.1c04626] [Citation(s) in RCA: 51] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/13/2023]
Abstract
This study explored whether the antiobesity effect of theabrownin (TB) extracted from Fu brick tea (FBT) was associated with the activation of brown adipose tissue (BAT) or browning of the white adipose tissue (WAT) in mice fed a high-fat diet (HFD). Mice were divided into five groups, which received a normal diet, HFD, or HFD plus TB (200, 400, and 800 mg/kg), respectively. A 12-week administration of TB in a dose-dependent manner reduced the body weight and WAT weight and improved lipid and glucose disorders in the HFD-fed mice (p < 0.05). TB also promoted the expression of thermogenic and mitochondrial genes, whereas inflammation genes were reduced in interscapular BAT (iBAT), inguinal WAT (iWAT), and epididymis white adipose tissue (eWAT), accompanied by improvement in the intestinal homeostasis by improving SCFAs, especially butyric acid levels (p < 0.05), which was related to thermogenic and inflammatory factors of iBAT and iWAT. Mechanistically, TB was shown to efficiently promote thermogenesis by stimulating the AMPK-PGC1α pathway with an increase in uncoupling protein 1 (UCP1). Conclusively, these findings suggest that long-term consumption of TB can enhance BAT activity and WAT browning by activating the AMPK-PGC1α pathway and modulating SCFAs; meanwhile, SCFAs regulating TB improved inflammatory disorder in HFD-fed mice.
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Affiliation(s)
- Yu Wang
- Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, and Shaanxi Key Laboratory for Hazard Factors Assessment in Processing and Storage of Agricultural Products, College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an 710119, China
| | - Aiqing Zhao
- Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, and Shaanxi Key Laboratory for Hazard Factors Assessment in Processing and Storage of Agricultural Products, College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an 710119, China
| | - Haiping Du
- Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, and Shaanxi Key Laboratory for Hazard Factors Assessment in Processing and Storage of Agricultural Products, College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an 710119, China
| | - Yueyue Liu
- Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, and Shaanxi Key Laboratory for Hazard Factors Assessment in Processing and Storage of Agricultural Products, College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an 710119, China
| | - Bangran Qi
- Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, and Shaanxi Key Laboratory for Hazard Factors Assessment in Processing and Storage of Agricultural Products, College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an 710119, China
| | - Xingbin Yang
- Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, and Shaanxi Key Laboratory for Hazard Factors Assessment in Processing and Storage of Agricultural Products, College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an 710119, China
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24
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Zhao J, Fang M, Xia Y. A liquid chromatography-mass spectrometry workflow for in-depth quantitation of fatty acid double bond location isomers. J Lipid Res 2021; 62:100110. [PMID: 34437891 PMCID: PMC8441088 DOI: 10.1016/j.jlr.2021.100110] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Revised: 08/11/2021] [Accepted: 08/12/2021] [Indexed: 01/31/2023] Open
Abstract
Tracing compositional changes of fatty acids (FAs) is frequently used as a means of monitoring metabolic alterations in perturbed biological states. Given that more than half of FAs in the mammalian lipidome are unsaturated, quantitation of FAs at a carbon-carbon double bond (C=C) location level is necessary. The use of 2-acetylpiridine (2-acpy) as the charge-tagging PB reagent led to a limit of identification in the subnanomolar range for mono- and polyunsaturated as well as conjugated FAs. Conjugated free FAs of low abundance such as FA 18:2 (n-7, n-9) and FA 18:2 (n-6, n-8) were quantified at concentrations of 0.61 ± 0.05 and 0.05 ± 0.01 mg per 100 g in yak milk powder, respectively. This workflow also enabled deep profiling of eight saturated and 37 unsaturated total FAs across a span of four orders of magnitude in concentration, including ten groups of C=C location isomers in pooled human plasma. A pilot survey on total FAs in plasma from patients with type 2 diabetes revealed that the relative compositions of FA 16:1 (n-10) and FA 18:1 (n-10) were significantly elevated compared with that of normal controls. In this work, we have developed a workflow for global quantitation of FAs, including C=C location isomers, via charge-tagging Paternò-Büchi (PB) derivatization and liquid chromatography-tandem mass spectrometry (LC-MS/MS).
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Affiliation(s)
- Jing Zhao
- MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Department of Chemistry, Tsinghua University, Beijing, China
| | - Mengxuan Fang
- MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Department of Chemistry, Tsinghua University, Beijing, China; School of Chemistry, University of Melbourne, Melbourne, Victoria, Australia
| | - Yu Xia
- MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Department of Chemistry, Tsinghua University, Beijing, China.
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25
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Yang F, Feng B, Niu YJ, Hu CY, Meng YH. Fu instant tea ameliorates fatty liver by improving microbiota dysbiosis and elevating short-chain fatty acids in the intestine of mice fed a high-fat diet. FOOD BIOSCI 2021. [DOI: 10.1016/j.fbio.2021.101207] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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26
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Du H, Wang Q, Li T, Ren D, Yang X. Grape seed proanthocyanidins reduced the overweight of C57BL/6J mice through modulating adipose thermogenesis and gut microbiota. Food Funct 2021; 12:8467-8477. [PMID: 34296715 DOI: 10.1039/d1fo01361k] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Activating the thermogenic function of adipocytes is an attractive therapeutic strategy against obesity and its associated metabolic complications. Proanthocyanidins are a class of polyphenols which are widely found in plants and daily foods. This aim of this study is to investigate the modulatory effects of grape seed proanthocyanidin extract (GSPE) on brown adipose tissue (BAT) activity, browning of white adipose tissue (WAT) and microbiome regulation in high-fat diet (HFD)-fed mice and its associated molecular mechanism. An 8-week administration of GSPE at 200 mg per kg bw in mice significantly reduced their final body weight, antagonized their HFD-induced insulin resistance and elevated their levels of adiponectin and leptin, respectively (p < 0.05). GSPE significantly increased the expression levels of thermogenic marker UCP1 in BAT and elevated the expression of a key transcription factor of browning, PRDM16, and thermogenic markers UCP1 and PGC-1α in inguinal white adipose tissue (iWAT). The high doses of GSPE also increased the levels of acetic acid, propionic acid and butyric acid in the colon of HFD-fed mice (p < 0.05). Furthermore, GSPE normalized the colonic Firmicutes/Bacteroidetes ratios, reversed the relative abundance of Weissella, Faecalibaculum, Bacteroides, Akkermansia and Ruminococcus 1 induced by HFD, and improved the structural diversity of the gut microbiota in C57BL/6J mice.
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Affiliation(s)
- Haiping Du
- Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, and Shaanxi Key Laboratory for Hazard Factors Assessment in Processing and Storage of Agricultural Products, College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an 710119, China.
| | - Qi Wang
- Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, and Shaanxi Key Laboratory for Hazard Factors Assessment in Processing and Storage of Agricultural Products, College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an 710119, China.
| | - Ting Li
- Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, and Shaanxi Key Laboratory for Hazard Factors Assessment in Processing and Storage of Agricultural Products, College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an 710119, China.
| | - Daoyuan Ren
- Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, and Shaanxi Key Laboratory for Hazard Factors Assessment in Processing and Storage of Agricultural Products, College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an 710119, China.
| | - Xingbin Yang
- Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, and Shaanxi Key Laboratory for Hazard Factors Assessment in Processing and Storage of Agricultural Products, College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an 710119, China.
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27
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Yin M, Matsuoka R, Xi Y, Wang X. Comparison of Egg Yolk and Soybean Phospholipids on Hepatic Fatty Acid Profile and Liver Protection in Rats Fed a High-Fructose Diet. Foods 2021; 10:1569. [PMID: 34359438 PMCID: PMC8307941 DOI: 10.3390/foods10071569] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2021] [Revised: 07/02/2021] [Accepted: 07/02/2021] [Indexed: 12/30/2022] Open
Abstract
Perturbed lipid metabolism leads to ectopic lipid accumulation in tissues, such as the liver, thereby causing nonalcoholic fatty liver disease (NAFLD) and negatively influencing circulating lipid profile-inducing dyslipidemia. Phospholipids (PLs) with special biological activity are used to treat chronic diseases such as cardiovascular and cerebrovascular disease. PLs derived from egg yolk and soya bean have significant antioxidant and lipid-lowering abilities. This study examined the therapeutic effects of them on hyperlipidemia using a high-fructose-fed rat model; lipid metabolism and anti-inflammatory effects were also analyzed. The results showed that both egg yolk and soya bean phospholipids (EPLs and SPLs) reduced liver weight, hepatic TG, and MDA content as well as serum ALT, AST, TBA, and CRP levels (p < 0.05). The PLs also showed hypolipidemic and anti-inflammatory effects. EPLs and SPLs could inhibit the accumulation of hepatic fatty acids C18:1N9C, C18:0, and C22:6NS of rats fed a high-fat-and-sucrose diet. The intake of EPLs could significantly increase acetylcholine content in the blood and brain tissue. Histological examination showed that PLs intake could ameliorate the damage to liver tissue. This study suggested that EPLs and SPLs had a certain capacity of hypolipidemic and liver protection, and the therapeutic benefits of EPLs tended to be more effective than that of soybean phospholipids.
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Affiliation(s)
- Mingyu Yin
- College of Food Science and Technology, Shanghai Ocean University, No. 999, Huchenghuan Rd, Nanhui New City, Pudong New District, Shanghai 201306, China
- Shanghai Engineering Research Center of Aquatic-Product Processing and Preservation, Shanghai 201306, China
| | - Ryosuke Matsuoka
- College of Food Science and Technology, Shanghai Ocean University, No. 999, Huchenghuan Rd, Nanhui New City, Pudong New District, Shanghai 201306, China
| | - Yinci Xi
- College of Food Science and Technology, Shanghai Ocean University, No. 999, Huchenghuan Rd, Nanhui New City, Pudong New District, Shanghai 201306, China
| | - Xichang Wang
- College of Food Science and Technology, Shanghai Ocean University, No. 999, Huchenghuan Rd, Nanhui New City, Pudong New District, Shanghai 201306, China
- Shanghai Engineering Research Center of Aquatic-Product Processing and Preservation, Shanghai 201306, China
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28
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Gholaminejad A, Fathalipour M, Roointan A. Comprehensive analysis of diabetic nephropathy expression profile based on weighted gene co-expression network analysis algorithm. BMC Nephrol 2021; 22:245. [PMID: 34215202 PMCID: PMC8252307 DOI: 10.1186/s12882-021-02447-2] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Accepted: 06/10/2021] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND Diabetic nephropathy (DN) is the major complication of diabetes mellitus, and leading cause of end-stage renal disease. The underlying molecular mechanism of DN is not yet completely clear. The aim of this study was to analyze a DN microarray dataset using weighted gene co-expression network analysis (WGCNA) algorithm for better understanding of DN pathogenesis and exploring key genes in the disease progression. METHODS The identified differentially expressed genes (DEGs) in DN dataset GSE47183 were introduced to WGCNA algorithm to construct co-expression modules. STRING database was used for construction of Protein-protein interaction (PPI) networks of the genes in all modules and the hub genes were identified considering both the degree centrality in the PPI networks and the ranked lists of weighted networks. Gene ontology and Reactome pathway enrichment analyses were performed on each module to understand their involvement in the biological processes and pathways. Following validation of the hub genes in another DN dataset (GSE96804), their up-stream regulators, including microRNAs and transcription factors were predicted and a regulatory network comprising of all these molecules was constructed. RESULTS After normalization and analysis of the dataset, 2475 significant DEGs were identified and clustered into six different co-expression modules by WGCNA algorithm. Then, DEGs of each module were subjected to functional enrichment analyses and PPI network constructions. Metabolic processes, cell cycle control, and apoptosis were among the top enriched terms. In the next step, 23 hub genes were identified among the modules in genes and five of them, including FN1, SLC2A2, FABP1, EHHADH and PIPOX were validated in another DN dataset. In the regulatory network, FN1 was the most affected hub gene and mir-27a and REAL were recognized as two main upstream-regulators of the hub genes. CONCLUSIONS The identified hub genes from the hearts of co-expression modules could widen our understanding of the DN development and might be of targets of future investigations, exploring their therapeutic potentials for treatment of this complicated disease.
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Affiliation(s)
- Alieh Gholaminejad
- Regenerative Medicine Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mohammad Fathalipour
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Amir Roointan
- Regenerative Medicine Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
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29
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Integrated metabolomics analysis of the effect of PPARδ agonist GW501516 on catabolism of BCAAs and carboxylic acids in diabetic mice. CHINESE CHEM LETT 2021. [DOI: 10.1016/j.cclet.2020.12.042] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
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30
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Zhang F, Guo R, Cui W, Wang L, Xiao J, Shang J, Zhao Z. Untargeted serum metabolomics and tryptophan metabolism profiling in type 2 diabetic patients with diabetic glomerulopathy. Ren Fail 2021; 43:980-992. [PMID: 34157945 PMCID: PMC8231361 DOI: 10.1080/0886022x.2021.1937219] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Diabetic glomerulopathy (DG) remains the prevalent microvascular complication and leading cause of shortened lifespan in type-2 diabetes mellitus (T2DM) despite improvement in hyperglycemia control. Considering the pivotal role of kidney in metabolism, using untargeted metabolomic techniques to globally delineate the serum metabolite profiles will help advance understanding pathogenetic underpinnings of renal biopsy-confirmed DG from the perspective of metabolism specifically. Fourteen pathologically diagnosed DG patients secondary to T2DM and 14 age- and gender-matched healthy controls (HCs) were recruited for study. We employed mass spectrometry-based untargeted metabolomic methods to reveal the metabolite profiles of serum samples collected from all included subjects. We identified a total of 334 and 397 metabolites in positive and negative ion mode respectively. One hundred and eighty-two important differential metabolites whose variable importance in projection (VIP) > 1 and p value <0.05 were selected and annotated to metabolic pathways. KEGG pathway enrichment analysis revealed tryptophan metabolism enriched most significantly. Among the tryptophan derivatives, L-tryptophan (L-Trp) and serotonin were relatively accumulated in DGs compared with HCs, while 5-hydroxyindoleacetic acid (5-HIAA) and indole-3-acetamide were depleted. Correlation analysis showed serotonin and L-Trp are negatively correlated with 24 h urine protein and glycosylated hemoglobin (Ghb). To exclude the interference of preexisting T2DM on DG exacerbation, we selected 5-HIAA and 3-(3-hydroxyphenyl) propionic acid (3-OHPPA) which are not correlated with Ghb and analyzed their correlation relationship with crucial renal indices. We found 3-OHPPA is positively correlated with urine total protein and creatinine ratio (T/Cr) and 24 h urine protein, 5-HIAA is positively correlated with serum creatinine and urea.
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Affiliation(s)
- Fanliang Zhang
- Department of Nephrology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China
| | - Ruixue Guo
- Department of Nephrology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China
| | - Wen Cui
- Department of Nephrology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China
| | - Li Wang
- Biobank of, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China
| | - Jing Xiao
- Department of Nephrology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China
| | - Jin Shang
- Department of Nephrology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China
| | - Zhanzheng Zhao
- Department of Nephrology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China
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31
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Sun N, Meng F, Zhao J, Li X, Li R, Han J, Chen X, Cheng W, Yang X, Kou Y, Zheng K, Yang J, Ikezoe T. Aurka deficiency in the intestinal epithelium promotes age-induced obesity via propionate-mediated AKT activation. Int J Biol Sci 2021; 17:1302-1314. [PMID: 33867847 PMCID: PMC8040479 DOI: 10.7150/ijbs.56477] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2020] [Accepted: 03/11/2021] [Indexed: 12/25/2022] Open
Abstract
Aurora-A kinase, a serine/threonine mitotic kinase involved in mitosis, is overexpressed in several human cancers. A recent study showed that Aurora-A mediates glucose metabolism via SOX8/FOXK1 in ovarian cancer. However, the roles of Aurora-A in metabolic diseases remain unclear. This study found that Aurka loss in the intestinal epithelium promoted age-induced obesity and enlargement of lipid droplets in parallel with an increase in infiltrated macrophages in the white adipocyte tissue (WAT) of male mice. Moreover, loss of Aurka induced the expression of lipid metabolism regulatory genes, including acetyl-coenzyme A carboxylase 1 (Acc1), in association with an increase in the levels of p-AKT in the intestinal epithelium as well as WAT. Blockade of AKT activation reduced the expression of lipid metabolism regulatory genes. In subsequent experiments, we found that the Firmicutes abundance and the levels of short-chain fatty acids (SCFAs) in the gut were dramatically increased in Aurkaf/+;VillinCre/+ mice compared with Aurkaf/+ mice. Additionally, propionate increased the phosphorylation of AKT in vitro. These observations indicated that Aurka loss in the intestinal epithelium contributed to gut microbiota dysbiosis and higher levels of SCFAs, especially propionate, leading to AKT activation and lipid metabolism regulatory gene expression, which in turn promoted age-induced obesity.
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Affiliation(s)
- Na Sun
- Jiangsu Province Key Laboratory of Immunity and Metabolism, Affiliated Hospital of Xuzhou Medical University.,Department of Pathogenic Biology and Immunology, Affiliated Hospital of Xuzhou Medical University
| | - Fandong Meng
- Department of Endocrinology, Affiliated Hospital of Xuzhou Medical University
| | - Jie Zhao
- Jiangsu Province Key Laboratory of Immunity and Metabolism, Affiliated Hospital of Xuzhou Medical University.,Department of Pathogenic Biology and Immunology, Affiliated Hospital of Xuzhou Medical University
| | - Xueqin Li
- Jiangsu Province Key Laboratory of Immunity and Metabolism, Affiliated Hospital of Xuzhou Medical University.,Department of Pathogenic Biology and Immunology, Affiliated Hospital of Xuzhou Medical University
| | - Rongqing Li
- Jiangsu Province Key Laboratory of Immunity and Metabolism, Affiliated Hospital of Xuzhou Medical University.,Department of Pathogenic Biology and Immunology, Affiliated Hospital of Xuzhou Medical University
| | - Jing Han
- Jiangsu Province Key Laboratory of Immunity and Metabolism, Affiliated Hospital of Xuzhou Medical University.,Department of Pathogenic Biology and Immunology, Affiliated Hospital of Xuzhou Medical University
| | - Xin Chen
- Jiangsu Province Key Laboratory of Immunity and Metabolism, Affiliated Hospital of Xuzhou Medical University.,Department of Pathogenic Biology and Immunology, Affiliated Hospital of Xuzhou Medical University
| | - Wanpeng Cheng
- Jiangsu Province Key Laboratory of Immunity and Metabolism, Affiliated Hospital of Xuzhou Medical University.,Department of Pathogenic Biology and Immunology, Affiliated Hospital of Xuzhou Medical University
| | - Xiaoying Yang
- Jiangsu Province Key Laboratory of Immunity and Metabolism, Affiliated Hospital of Xuzhou Medical University.,Department of Pathogenic Biology and Immunology, Affiliated Hospital of Xuzhou Medical University
| | - Yanbo Kou
- Jiangsu Province Key Laboratory of Immunity and Metabolism, Affiliated Hospital of Xuzhou Medical University.,Department of Pathogenic Biology and Immunology, Affiliated Hospital of Xuzhou Medical University
| | - Kuiyang Zheng
- Jiangsu Province Key Laboratory of Immunity and Metabolism, Affiliated Hospital of Xuzhou Medical University.,Department of Pathogenic Biology and Immunology, Affiliated Hospital of Xuzhou Medical University.,National Experimental Demonstration Center for Basic Medicine Education, Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Jing Yang
- Jiangsu Province Key Laboratory of Immunity and Metabolism, Affiliated Hospital of Xuzhou Medical University.,Department of Pathogenic Biology and Immunology, Affiliated Hospital of Xuzhou Medical University.,National Experimental Demonstration Center for Basic Medicine Education, Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Takayuki Ikezoe
- The Department of Hematology, Fukushima Medical University, Fukushima, Japan
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32
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Gradisteanu Pircalabioru G, Corcionivoschi N, Gundogdu O, Chifiriuc MC, Marutescu LG, Ispas B, Savu O. Dysbiosis in the Development of Type I Diabetes and Associated Complications: From Mechanisms to Targeted Gut Microbes Manipulation Therapies. Int J Mol Sci 2021; 22:2763. [PMID: 33803255 PMCID: PMC7967220 DOI: 10.3390/ijms22052763] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2021] [Revised: 03/06/2021] [Accepted: 03/08/2021] [Indexed: 12/12/2022] Open
Abstract
Globally, we are facing a worrying increase in type 1 diabetes mellitus (T1DM) incidence, with onset at younger age shedding light on the need to better understand the mechanisms of disease and step-up prevention. Given its implication in immune system development and regulation of metabolism, there is no surprise that the gut microbiota is a possible culprit behind T1DM pathogenesis. Additionally, microbiota manipulation by probiotics, prebiotics, dietary factors and microbiota transplantation can all modulate early host-microbiota interactions by enabling beneficial microbes with protective potential for individuals with T1DM or at high risk of developing T1DM. In this review, we discuss the challenges and perspectives of translating microbiome data into clinical practice. Nevertheless, this progress will only be possible if we focus our interest on developing numerous longitudinal, multicenter, interventional and double-blind randomized clinical trials to confirm their efficacy and safety of these therapeutic approaches.
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Affiliation(s)
| | - Nicolae Corcionivoschi
- Bacteriology Branch, Veterinary Sciences Division, Agri-Food and Biosciences Institute, Belfast BT9 5PX, UK;
| | - Ozan Gundogdu
- Faculty of Infectious & Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK;
| | - Mariana-Carmen Chifiriuc
- Research Institute of University of Bucharest (ICUB), 300645 Bucharest, Romania; (G.G.P.); (L.G.M.); (B.I.)
- Academy of Romanian Scientists, 050045 Bucharest, Romania
| | | | - Bogdan Ispas
- Research Institute of University of Bucharest (ICUB), 300645 Bucharest, Romania; (G.G.P.); (L.G.M.); (B.I.)
| | - Octavian Savu
- “N.C. Paulescu” National Institute of Diabetes, Nutrition and Metabolic Diseases, 2nd District, 020042 Bucharest, Romania;
- Department of Doctoral School, “Carol Davila” University of Medicine and Pharmacy, 5th District, 050474 Bucharest, Romania
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33
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Eriksen F, Carlsson ER, Munk JK, Madsbad S, Fenger M. Fractionated free fatty acids and their relation to diabetes status after Roux-en-Y gastric bypass: A cohort study. Physiol Rep 2021; 9:e14708. [PMID: 33463892 PMCID: PMC7814490 DOI: 10.14814/phy2.14708] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2020] [Revised: 12/11/2020] [Accepted: 12/12/2020] [Indexed: 01/15/2023] Open
Abstract
Bariatric surgery is associated with near-immediate remission of type 2 diabetes and recently suggested as a treatment for type 2 diabetes. Specifically, Roux-en-Y gastric bypass has been a focus of much research, but still, the mechanisms of action are only partly elucidated. We aim to investigate whether some mechanisms might be mediated by free fatty acids (FFAs). We measured eight fractionated FFAs before and up to 2 years after Roux-en-Y gastric bypass surgery in 207 patients, divided into three groups. One non-diabetic group, one diabetic group with post-operative remission and one diabetic group with persistent diabetes after surgery. Pre- and postoperative levels of fractionated FFAs were compared within and between groups. The sum of the measured FFAs were lower in the group with persistent diabetes, compared to the other groups. The pre-surgery level of linoleic acid in the group with persistent diabetes was significantly lower compared to the other two groups. The levels of fractionated FFAs decreased from pre-surgery to three months after surgery, except for oleic acid and arachidonic acid and for Docosahexaenoic acid (DHA) in the non-diabetic group. The FFAs with decreasing levels from pre-surgery to three months post-surgery are all precursors to oleic acid, arachidonic acid, and DHA, respectively, which may imply a drift, indicating that they need to be sustained at an acceptable level for optimal metabolic function. The fact that the sum of the measured FFAs is lower in the group with persistent diabetes may suggest that this group and the group with diabetes remission represent two distinct types of type 2 diabetes. It is proposed that linoleic acid could be used as a biomarker to determine the plausibility for type 2 diabetes remission after Roux-en-Y gastric bypass surgery.
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Affiliation(s)
- Freja Eriksen
- Department of Clinical BiochemistryCopenhagen University Hospital HvidovreHvidovreDenmark
| | - Elin R. Carlsson
- Department of Clinical BiochemistryCopenhagen University Hospital HvidovreHvidovreDenmark
- Department of Clinical BiochemistryNordsjaellands HospitalUniversity of CopenhagenHillerodDenmark
| | - Jens K. Munk
- Department of Clinical BiochemistryCopenhagen University Hospital HvidovreHvidovreDenmark
| | - Sten Madsbad
- Department of EndocrinologyCopenhagen University Hospital HvidovreHvidovreDenmark
| | - Mogens Fenger
- Department of Clinical BiochemistryCopenhagen University Hospital HvidovreHvidovreDenmark
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34
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Liu X, Zhao K, Jing N, Zhao Y, Yang X. EGCG regulates fatty acid metabolism of high-fat diet-fed mice in association with enrichment of gut Akkermansia muciniphila. J Funct Foods 2020. [DOI: 10.1016/j.jff.2020.104261] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
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35
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Wu ZE, Fraser K, Kruger MC, Sequeira IR, Yip W, Lu LW, Plank LD, Murphy R, Cooper GJS, Martin JC, Poppitt SD. Metabolomic signatures for visceral adiposity and dysglycaemia in Asian Chinese and Caucasian European adults: the cross-sectional TOFI_Asia study. Nutr Metab (Lond) 2020; 17:95. [PMID: 33292338 PMCID: PMC7667766 DOI: 10.1186/s12986-020-00518-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Accepted: 10/20/2020] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Asian Chinese are more susceptible to deposition of visceral adipose tissue (VAT) and type 2 diabetes (T2D) development than European Caucasians when matched for gender, age and body mass index (BMI). Our aims were: (i) characterise the ethnicity-specific metabolomic signature of visceral adiposity measured by dual energy X-ray absorptiometry (DXA) and fasting plasma glucose (FPG), and (ii) identify individuals susceptible to worse metabolic health outcomes. METHODS Fasting plasma samples from normoglycaemic (n = 274) and prediabetic (n = 83) participants were analysed with liquid chromatography-mass spectrometry using untargeted metabolomics. Multiple linear regression adjusting for age, gender and BMI was performed to identify metabolites associated with FPG and VAT calculated as percentage of total body fat (%VATTBF) in each ethnic group. Metabolic risk groups in each ethnicity were stratified based on the joint metabolomic signature for FPG and %VATTBF and clinically characterised using partial least squares-discriminant analysis (PLS-DA) and t-tests. RESULTS FPG was correlated with 40 and 110 metabolites in Caucasians and Chinese respectively, with diglyceride DG(38:5) (adjusted β = 0.29, p = 3.00E-05) in Caucasians and triglyceride TG(54:4) (adjusted β = 0.28, p = 2.02E-07) in Chinese being the most significantly correlated metabolite based on the p-value. %VATTBF was correlated with 85 and 119 metabolites in Caucasians and Chinese respectively, with TG(56:2) (adjusted β = 0.3, p = 8.25E-09) in Caucasians and TG(58:3) (adjusted β = 0.25, p = 2.34E-08) in Chinese being the most significantly correlated. 24 metabolites associated with FPG were common to both ethnicities including glycerolipid species. 67 metabolites associated with %VATTBF were common to both ethnicities including positive correlations with dihydroceramide, sphingomyelin, glycerolipid, phosphatidylcholine, phosphatidylethnolamine, and inverse correlations with ether-linked phosphatidylcholine. Participant re-stratification found greater total and central adiposity, worse clinical lipid profiles, higher serum glucoregulatory peptides and liver enzymes in normal fasting glucose (NFG) individuals with a prediabetic metabolomic profile than NFG individuals with a normoglycaemic metabolomic profile in both ethnicities. CONCLUSIONS Untargeted metabolomics identified common and disparate metabolites associated with FPG and %VATTBF, with an ethnic-dimorphic signature for these metabolic traits. These signatures could improve risk stratification and identify NFG individuals with an adverse cardiometabolic and T2D risk profile.
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Affiliation(s)
- Zhanxuan E Wu
- Food Nutrition and Health, Food and Bio-Based Products, AgResearch Limited, Palmerston North, 4442, New Zealand.,School of Health Sciences, Massey University, Palmerston North, 4442, New Zealand.,High-Value Nutrition National Science Challenge, Auckland, New Zealand
| | - Karl Fraser
- Food Nutrition and Health, Food and Bio-Based Products, AgResearch Limited, Palmerston North, 4442, New Zealand. .,High-Value Nutrition National Science Challenge, Auckland, New Zealand. .,Riddet Institute, Massey University, Palmerston North, 4442, New Zealand.
| | - Marlena C Kruger
- School of Health Sciences, Massey University, Palmerston North, 4442, New Zealand.,Riddet Institute, Massey University, Palmerston North, 4442, New Zealand
| | - Ivana R Sequeira
- High-Value Nutrition National Science Challenge, Auckland, New Zealand.,Human Nutrition Unit, School of Biological Sciences, University of Auckland, Auckland, 1010, New Zealand
| | - Wilson Yip
- High-Value Nutrition National Science Challenge, Auckland, New Zealand.,Human Nutrition Unit, School of Biological Sciences, University of Auckland, Auckland, 1010, New Zealand
| | - Louise W Lu
- High-Value Nutrition National Science Challenge, Auckland, New Zealand.,Human Nutrition Unit, School of Biological Sciences, University of Auckland, Auckland, 1010, New Zealand
| | - Lindsay D Plank
- Department of Surgery, University of Auckland, Auckland, 1010, New Zealand
| | - Rinki Murphy
- High-Value Nutrition National Science Challenge, Auckland, New Zealand.,Department of Medicine, School of Biological Sciences, University of Auckland, Auckland, 1010, New Zealand
| | - Garth J S Cooper
- Department of Medicine, School of Biological Sciences, University of Auckland, Auckland, 1010, New Zealand.,Centre for Advanced Discovery and Experimental Therapeutics, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, M13 9NT, UK
| | | | - Sally D Poppitt
- High-Value Nutrition National Science Challenge, Auckland, New Zealand.,Riddet Institute, Massey University, Palmerston North, 4442, New Zealand.,Human Nutrition Unit, School of Biological Sciences, University of Auckland, Auckland, 1010, New Zealand.,Department of Medicine, School of Biological Sciences, University of Auckland, Auckland, 1010, New Zealand
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Cordero-Pérez P, Sánchez-Martínez C, García-Hernández PA, Saucedo AL. Metabolomics of the diabetic nephropathy: behind the fingerprint of development and progression indicators. Nefrologia 2020; 40:585-596. [PMID: 33036786 DOI: 10.1016/j.nefro.2020.07.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2019] [Revised: 06/24/2020] [Accepted: 07/05/2020] [Indexed: 01/01/2023] Open
Abstract
Current diagnostic methods are not very sensitive to detect the initial stages diabetic nephropathy of type 2. In this work, a review of metabolomic approximation studies for the identification of biomarkers of this disease with potential to differentiate between early stages, evaluate and direct treatment and help slow kidney damage. Using public (Pubmed and Google Scholar) and private (Scopus and Web of Knowledge) databases, a systematic search of the information published related to metabolomics of diabetic nephropathy in different biospecimens (urine, serum, plasma and blood) was made. Later, the MetaboAnalyst 4.0 software was used to identify the metabolic pathways associated with these metabolites. Groups of potential metabolites were identified for monitoring diabetic nephropathy with the available literature data. In the urine, oxide-3-hydroxyisovalerate, TMAO, aconite and citrate and hydroxypropionate derivatives are highlighted; meanwhile, in the serum: citrate, creatinine, arginine and its derivatives; and in the plasma: amino acids such as histidine, methionine and arginine has a potential contribution. Using MetaboAnalyst 4.0 the metabolic pathways related to these metabolites were related. The search for biomarkers to measure the progression of diabetic nephropathy, together with analytical strategies for their detection and quantification, are the starting point for designing new methods of clinical chemistry analysis. The association between the metabolic pathway dysfunction could be useful for the overall assessment of the treatment and clinical follow-up of this disease.
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Affiliation(s)
- Paula Cordero-Pérez
- Unidad de Hígado, Hospital Universitario "Dr. José Eleuterio González", Universidad Autónoma de Nuevo León, Monterrey, NL, México
| | - Concepción Sánchez-Martínez
- Centro Regional de Enfermedades Renales, Hospital Universitario "Dr. José Eleuterio González", Universidad Autónoma de Nuevo León, Monterrey, NL, México
| | - Pedro Alberto García-Hernández
- Servicio de Endocrinología, Hospital Universitario "Dr. José Eleuterio González", Universidad Autónoma de Nuevo León, Monterrey, NL, México
| | - Alma L Saucedo
- Departamento de Química Analítica, Facultad de Medicina, Universidad Autónoma de Nuevo León, Monterrey, NL, México; Consejo Nacional de Ciencia y Tecnología, Cátedras CONACYT, Ciudad de México, México.
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Lolli V, Dall’Asta M, Del Rio D, Caligiani A. Identification of Cyclopropane Fatty Acids in Human Plasma after Controlled Dietary Intake of Specific Foods. Nutrients 2020; 12:nu12113347. [PMID: 33143177 PMCID: PMC7693023 DOI: 10.3390/nu12113347] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Revised: 10/26/2020] [Accepted: 10/27/2020] [Indexed: 11/21/2022] Open
Abstract
Cyclopropane fatty acids (CPFAs) are an investigated class of secondary fatty acids of microbial origin recently identified in foods. Even though the dietary daily intake of this class of compounds it has been recently estimated as not negligible, to date, no studies specifically have investigated their presence in human plasma after consumption of CPFA-rich sources. Therefore, the aims of this study were (i) to test CPFAs concentration in human plasma, thus demonstrating their in vivo bioaccessibility and potential bioavailability, (ii) to investigate a dose-response relationship between medium term chronic intake of CPFAs-rich foods and both CPFAs and plasma total fatty acid profiles in healthy subjects. Ten healthy normal weight adults were enrolled for conducting an in vivo study. Participants were asked to follow a CPFA-controlled diet for 3 weeks, consuming 50 g of Grana Padano cheese (GP) and 250 mL of whole cow milk, which correspond to a total of 22.1 mg of CPFAs. Fasting CPFAs concentration were monitored for eight timepoints during the whole study and plasma total fatty acids composition was determined by GC-MS. CPFAs, mainly dihydrosterculic acid (DHSA), were identified in plasma total fatty acids profile at the beginning of the study and after dietary treatment. A significant (p < 0.05) increase of CPFAs mean plasma concentration (n = 10) were observed at the end of the dietary intervention. Contrarily, the total fatty acids composition of the general plasma fatty acids profile did not significantly change (p ≥ 0.05) during the dietary intervention period. This is the first investigation demonstrating that CPFAs are bioaccessible in vivo and, as expected, their plasmatic concentration may be affected by consumption of CPFAs-rich foods. This research will open the door to further detailed research, which may better elucidate the role of these compounds in human health.
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Affiliation(s)
- Veronica Lolli
- Department of Food and Drug, University of Parma, 43124 Parma, Italy; (V.L.); (A.C.)
| | - Margherita Dall’Asta
- Department of Animal Science, Food and Nutrition, Università Cattolica del Sacro Cuore, 29122 Piacenza, Italy
- Correspondence:
| | - Daniele Del Rio
- Department of Veterinary Science, University of Parma, 43126 Parma, Italy;
- School of Advanced Studies on Food and Nutrition, University of Parma, 43124 Parma, Italy
| | - Augusta Caligiani
- Department of Food and Drug, University of Parma, 43124 Parma, Italy; (V.L.); (A.C.)
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38
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Sun L, Zong G, Li H, Lin X. Fatty acids and cardiometabolic health: a review of studies in Chinese populations. Eur J Clin Nutr 2020; 75:253-266. [PMID: 32801302 DOI: 10.1038/s41430-020-00709-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2020] [Revised: 06/19/2020] [Accepted: 08/04/2020] [Indexed: 11/09/2022]
Abstract
Rapid nutrition transition from plant-based traditional diet to westernized diet has led to dramatically heightening burdens of cardiometabolic diseases in China in past decades. Recently, national surveys reported that poor dietary quality including low marine n-3 fatty acids and high intakes of red meat and processed meat was associated with considerably elevated cardiometabolic deaths. Previous studies mainly from Western population-based cohorts have indicated that not only fat quantity but also quality linked with different cardiometabolic outcomes. Compared with Western peoples, Asian peoples, including Chinese, are known to have different dietary patterns and lifestyle, as well as genetic heterogeneities, which may modify fatty acid metabolism and disease susceptibility in certain degree. To date, there were limited prospective studies investigating the relationships between fatty acids and cardiometabolic disease outcomes in Chinese, and most existing studies were cross-sectional nature and within one or two region(s). Notably, shifting dietary patterns could change not only amount, types, and ratio of fatty acids accounting for overall energy intake, but also their food sources and ratio to other macronutrients. Moreover, large geographic and urban-rural variations in prevalence of cardiometabolic diseases among Chinese may also reflect the effects of socioeconomic development and local diets on health status. Therefore, current review will summarize available literatures with more focus on the Chinese-based studies which may extend current knowledge about the roles of fatty acids in pathogenesis of cardiometabolic diseases for Asian populations and also provide useful information for trans-ethnic comparisons with other populations.
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Affiliation(s)
- Liang Sun
- CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China
| | - Geng Zong
- CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China
| | - Huaixing Li
- CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China
| | - Xu Lin
- Key Laboratory of Systems Biology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Hangzhou, 310024, China. .,Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
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Su Y, Chen Q, Ju Y, Li W, Li W. Palmitate induces human glomerular mesangial cells fibrosis through CD36-mediated transient receptor potential canonical channel 6/nuclear factor of activated T cell 2 activation. Biochim Biophys Acta Mol Cell Biol Lipids 2020; 1865:158793. [PMID: 32800850 DOI: 10.1016/j.bbalip.2020.158793] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Revised: 08/06/2020] [Accepted: 08/09/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Our previous study suggested that palmitate (PA) induces human glomerular mesangial cells (HMCs) fibrosis. However, the mechanism is not fully understood. Recent studies suggested that transient receptor potential canonical channel 6 (TRPC6)/nuclear factor of activated T cell 2 (NFAT2) played an important role in renal fibrosis. Moreover, cluster of differentiation 36 (CD36) regulated the synthesis of TPRC6 agonist diglyceride. In the present study, we investigated whether PA induced HMCs fibrosis via TRPC6/NFAT2 mediated by CD36. METHODS A type 2 diabetic nephropathy (DN) model was established in Sprague Dawley rats, and HMCs were stimulated with PA. Lipid accumulation and free fatty acid (FFA) uptake were measured. The expression levels of TGF-β1, p-Smad2/3, FN, TRPC6, NFAT2 and CD36 were evaluated. The intracellular calcium concentration ([Ca2+]i) was assessed. RESULTS FFA were elevated in type 2 DN rats with kidney fibrosis in addition to NFAT2 and CD36 expression. In vitro, PA induced HMCs fibrosis, [Ca2+]i elevation and NFAT2 activation. SKF96365 or TRPC6-siRNA could attenuate PA-induced HMCs damage. By contrast, the TRPC6 activator showed the opposite effect. Moreover, NFAT2-siRNA also suppressed PA-induced HMCs fibrosis. CD36 knockdown inhibited the PA-induced [Ca2+]i elevation and NFAT2 expression. In addition, long-term treatment with PA decreased TRPC6 expression in HMCs. CONCLUSION The results of this study demonstrated that PA could induce the activation of the [Ca2+]i/NFAT2 signaling pathway through TRPC6, which led to HMCs fibrosis. Although activation of TRPC6 attributed to CD36-mediated lipid deposition, long-term stimulation of PA may lead to negative feedback on the expression of TPRC6.
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Affiliation(s)
- Yong Su
- Department of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, Anhui, China; Key Laboratory of Anti-Inflammatory and Immunopharmacology, Ministry of Education, Department of Pharmacology, Anhui Medical University, Hefei 230032, Anhui, China
| | - Qingqing Chen
- Key Laboratory of Anti-Inflammatory and Immunopharmacology, Ministry of Education, Department of Pharmacology, Anhui Medical University, Hefei 230032, Anhui, China
| | - Yinghui Ju
- Department of Pharmacy, Hefei Ion Medical Center, Hefei 230032, Anhui, China
| | - Weizu Li
- Key Laboratory of Anti-Inflammatory and Immunopharmacology, Ministry of Education, Department of Pharmacology, Anhui Medical University, Hefei 230032, Anhui, China.
| | - Weiping Li
- Key Laboratory of Anti-Inflammatory and Immunopharmacology, Ministry of Education, Department of Pharmacology, Anhui Medical University, Hefei 230032, Anhui, China; Anqing Medical and Pharmaceutical College, Anqing 246052, Anhui, China.
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40
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Azab SM, de Souza RJ, Teo KK, Anand SS, Williams NC, Holzschuher J, McGlory C, Philips SM, Britz-McKibbin P. Serum nonesterified fatty acids have utility as dietary biomarkers of fat intake from fish, fish oil, and dairy in women. J Lipid Res 2020; 61:933-944. [PMID: 32234835 PMCID: PMC7269757 DOI: 10.1194/jlr.d120000630] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Revised: 03/26/2020] [Indexed: 12/16/2022] Open
Abstract
Nutritional studies rely on various biological specimens for FA determination, yet it is unclear how levels of serum NEFAs correlate with other circulating lipid pools. Here, we used a high-throughput method (<4 min/sample) based on multisegment injection-nonaqueous capillary electrophoresis-mass spectrometry (MSI-NACE-MS) to investigate whether specific serum NEFAs have utility as biomarkers of dietary fat intake in women. We first identified circulating NEFAs correlated with long-term/habitual food intake among pregnant women with contrasting dietary patterns (n = 50). Acute changes in serum NEFA trajectories were also studied in nonpregnant women (n = 18) following high-dose (5 g/day) fish oil (FO) supplementation or isoenergetic sunflower oil placebo over 56 days. In the cross-sectional study, serum ω-3 FAs correlated with self-reported total ω-3 daily intake, notably EPA as its NEFA (r = 0.46; P = 0.001), whereas pentadecanoic acid was associated with full-fat dairy intake (r = 0.43; P = 0.002), outcomes consistent with results from total FA serum hydrolysates. In the intervention cohort, serum ω-3 NEFAs increased 2.5-fold from baseline within 28 days following FO supplementation, and this increase was most pronounced for EPA (P = 0.0004). Unlike for DHA, circulating EPA as its NEFA also strongly correlated to EPA concentrations measured from erythrocyte phospholipid hydrolysates (r = 0.66; P = 4.6 × 10-10) and was better suited to detect dietary nonadherence. We conclude that MSI-NACE-MS offers a rapid method to quantify serum NEFAs and objectively monitor dietary fat intake in women that is complementary to food-frequency questionnaires.
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Affiliation(s)
- Sandi M Azab
- Departments of Chemistry and Chemical Biology, McMaster University, Hamilton, ON, Canada; Department of Pharmacognosy, Alexandria University, Alexandria, Egypt
| | - Russell J de Souza
- Medicine, McMaster University, Hamilton, ON, Canada; Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada
| | - Koon K Teo
- Medicine, McMaster University, Hamilton, ON, Canada
| | - Sonia S Anand
- Medicine, McMaster University, Hamilton, ON, Canada; Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada
| | | | - Jordan Holzschuher
- Departments of Chemistry and Chemical Biology, McMaster University, Hamilton, ON, Canada
| | - Chris McGlory
- Kinesiology, McMaster University, Hamilton, ON, Canada
| | | | - Philip Britz-McKibbin
- Departments of Chemistry and Chemical Biology, McMaster University, Hamilton, ON, Canada. mailto:
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41
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Omics research in diabetic kidney disease: new biomarker dimensions and new understandings? J Nephrol 2020; 33:931-948. [DOI: 10.1007/s40620-020-00759-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2020] [Accepted: 05/23/2020] [Indexed: 12/14/2022]
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Lin D, Jiang X, Zhao Y, Zhai X, Yang X. Komagataeibacter hansenii CGMCC 3917 alleviates alcohol-induced liver injury by regulating fatty acid metabolism and intestinal microbiota diversity in mice. Food Funct 2020; 11:4591-4604. [PMID: 32432239 DOI: 10.1039/c9fo02040c] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
The potential effects of Komagataeibacter hansenii CGMCC 3917 cells on alcohol-induced liver injury and their probable mechanisms were investigated. Male Kunming mice were orally administered with alcohol (10 mL per kg BW) alone or in combination with administration of K. hansenii CGMCC 3917 cells at 2 × 108 and 2 × 106 CFUs for 10 weeks. Administration of strain CGMCC 3917 cells, especially high dose administration, decreased the liver weights, fat gain, and fatty-acid metabolism-related enzyme SCD-1, ACC and FAS expressions and endotoxin release, which were elevated by alcohol treatment. Furthermore, the total contents of long chain fatty acids of the liver and serum in alcohol-treated mice supplemented with a high dose of strain CGMCC 3917 cells were decreased to 5.44 ± 0.19 μg mL-1 and 3.66 ± 0.15 μg mL-1 from 6.65 ± 0.31 μg mL-1 and 4.52 ± 0.21 μg mL-1, respectively. Conversely, the SCFAs decreased by ethanol treatment, particularly the acetic acid, propionic acid and butyric acid, were obviously enhanced in the faeces, colon and cecum of the mice supplemented with strain CGMCC 3917 cells. Moreover, strain CGMCC 3917 cells could regulate gut microbiome by significantly decreasing the abundance of Actinobacteria, Proteobacteria and Firmicutes, and dramatically increasing the abundance of Bacteroidetes in alcohol-treated mice. These findings suggest that K. hansenii CGMCC 3917 cells alleviate alcohol-induced liver damage via regulating fatty acid metabolism and intestinal microbiota diversity in mice.
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Affiliation(s)
- Dehui Lin
- Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, and Shaanxi Key Laboratory for Hazard Factors Assessment in Processing and Storage of Agricultural Products, College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an 710119, China.
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Opazo-Ríos L, Mas S, Marín-Royo G, Mezzano S, Gómez-Guerrero C, Moreno JA, Egido J. Lipotoxicity and Diabetic Nephropathy: Novel Mechanistic Insights and Therapeutic Opportunities. Int J Mol Sci 2020; 21:E2632. [PMID: 32290082 PMCID: PMC7177360 DOI: 10.3390/ijms21072632] [Citation(s) in RCA: 201] [Impact Index Per Article: 40.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2020] [Revised: 04/07/2020] [Accepted: 04/08/2020] [Indexed: 02/06/2023] Open
Abstract
Lipotoxicity is characterized by the ectopic accumulation of lipids in organs different from adipose tissue. Lipotoxicity is mainly associated with dysfunctional signaling and insulin resistance response in non-adipose tissue such as myocardium, pancreas, skeletal muscle, liver, and kidney. Serum lipid abnormalities and renal ectopic lipid accumulation have been associated with the development of kidney diseases, in particular diabetic nephropathy. Chronic hyperinsulinemia, often seen in type 2 diabetes, plays a crucial role in blood and liver lipid metabolism abnormalities, thus resulting in increased non-esterified fatty acids (NEFA). Excessive lipid accumulation alters cellular homeostasis and activates lipogenic and glycogenic cell-signaling pathways. Recent evidences indicate that both quantity and quality of lipids are involved in renal damage associated to lipotoxicity by activating inflammation, oxidative stress, mitochondrial dysfunction, and cell-death. The pathological effects of lipotoxicity have been observed in renal cells, thus promoting podocyte injury, tubular damage, mesangial proliferation, endothelial activation, and formation of macrophage-derived foam cells. Therefore, this review examines the recent preclinical and clinical research about the potentially harmful effects of lipids in the kidney, metabolic markers associated with these mechanisms, major signaling pathways affected, the causes of excessive lipid accumulation, and the types of lipids involved, as well as offers a comprehensive update of therapeutic strategies targeting lipotoxicity.
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Affiliation(s)
- Lucas Opazo-Ríos
- Renal, Vascular and Diabetes Research Laboratory, IIS-Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), 28040 Madrid, Spain; (L.O.-R.); (G.M.-R.); (C.G.-G.); (J.E.)
| | - Sebastián Mas
- Renal, Vascular and Diabetes Research Laboratory, IIS-Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), 28040 Madrid, Spain; (L.O.-R.); (G.M.-R.); (C.G.-G.); (J.E.)
| | - Gema Marín-Royo
- Renal, Vascular and Diabetes Research Laboratory, IIS-Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), 28040 Madrid, Spain; (L.O.-R.); (G.M.-R.); (C.G.-G.); (J.E.)
| | - Sergio Mezzano
- Laboratorio de Nefrología, Facultad de Medicina, Universidad Austral de Chile, 5090000 Valdivia, Chile;
| | - Carmen Gómez-Guerrero
- Renal, Vascular and Diabetes Research Laboratory, IIS-Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), 28040 Madrid, Spain; (L.O.-R.); (G.M.-R.); (C.G.-G.); (J.E.)
| | - Juan Antonio Moreno
- Department of Cell Biology, Physiology and Immunology, University of Cordoba, 14004 Cordoba, Spain
- Maimonides Biomedical Research Institute of Cordoba (IMIBIC), University of Cordoba, 14004 Cordoba, Spain
- Hospital Universitario Reina Sofía, 14004 Cordoba, Spain
| | - Jesús Egido
- Renal, Vascular and Diabetes Research Laboratory, IIS-Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), 28040 Madrid, Spain; (L.O.-R.); (G.M.-R.); (C.G.-G.); (J.E.)
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Alim A, Li T, Nisar T, Ren D, Liu Y, Yang X. Consumption of two whole kiwifruit (Actinide chinensis) per day improves lipid homeostasis, fatty acid metabolism and gut microbiota in healthy rats. Int J Biol Macromol 2020; 156:186-195. [PMID: 32278604 DOI: 10.1016/j.ijbiomac.2020.04.028] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2020] [Revised: 03/27/2020] [Accepted: 04/05/2020] [Indexed: 02/08/2023]
Abstract
Golden kiwifruit (Actinidia chinensis) peel is a by-product enriched with polyphenols. The effects of fleshes of two Actinidia chinensis fruits (ACF) and fleshes with peels of two Actinidia chinensis fruits (ACFP) on lipid homeostasis, fatty acid metabolism and gut microbiota was investigated in healthy rats. Intervention of ACF and ACFP for 4 weeks significantly reduced total cholesterol, total triglycerides, and increased the high-density lipoprotein levels in rats. ACF and ACFP ameliorated lipid peroxidation in rats, by the lowering hepatic MDA level and enhancing GSH-Px and SOD activities. In addition, ACFP significantly decreased the saturated fatty acids in serum and increased the polyunsaturated fatty acids in hepatic and serum of rats. Analysis of gut microbiota revealed that ACF and ACFP evidently increased the microbial richness and diversity of gut microbiota. The Firmicutes/Bacteroidetes ratio was significantly reduced from 3.04 in ND group to 1.34 and 2.12 in ACF and ACFP groups, respectively. Moreover, ACF and ACFP significantly increased the abundance of beneficial bacteria (Lactobacillus and Barnesiella) and reduced harmful bacteria (Enterococcus, Escherichia, and Staphylococcus). Overall, ACFP exerts more potent health-improving effects than ACF. Our study provides a scientific basis for the development of kiwifruit (including pericarp)-based novel natural products with significant health benefits.
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Affiliation(s)
- Aamina Alim
- Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, Shaanxi Key Laboratory for Hazard Factors Assessment in Processing and Storage of Agricultural Products, College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an 710119, China
| | - Ting Li
- Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, Shaanxi Key Laboratory for Hazard Factors Assessment in Processing and Storage of Agricultural Products, College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an 710119, China.
| | - Tanzeela Nisar
- Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, Shaanxi Key Laboratory for Hazard Factors Assessment in Processing and Storage of Agricultural Products, College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an 710119, China
| | - Daoyuan Ren
- Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, Shaanxi Key Laboratory for Hazard Factors Assessment in Processing and Storage of Agricultural Products, College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an 710119, China
| | - Yueyue Liu
- Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, Shaanxi Key Laboratory for Hazard Factors Assessment in Processing and Storage of Agricultural Products, College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an 710119, China
| | - Xingbin Yang
- Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, Shaanxi Key Laboratory for Hazard Factors Assessment in Processing and Storage of Agricultural Products, College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an 710119, China.
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45
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Shi H, Wang Q, Zheng M, Hao S, Lum JS, Chen X, Huang XF, Yu Y, Zheng K. Supplement of microbiota-accessible carbohydrates prevents neuroinflammation and cognitive decline by improving the gut microbiota-brain axis in diet-induced obese mice. J Neuroinflammation 2020; 17:77. [PMID: 32127019 PMCID: PMC7055120 DOI: 10.1186/s12974-020-01760-1] [Citation(s) in RCA: 80] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2019] [Accepted: 02/26/2020] [Indexed: 12/18/2022] Open
Abstract
Background Western pattern diets induce neuroinflammation and impair cognitive behavior in humans and animals. Neuroinflammation and cognitive impairment have been associated with microbiota dysbiosis, through the gut-brain axis. Furthermore, microbiota-accessible carbohydrates (MACs) found in dietary fiber are important in shaping the microbial ecosystem and have the potential to improve the gut-brain-axis. However, the effects of MACs on neuroinflammation and cognition in an obese condition have not yet been investigated. The present study aimed to evaluate the effect of MACs on the microbiota-gut-brain axis and cognitive function in obese mice induced by a high-fat and fiber deficient (HF-FD) diet. Methods C57Bl/6 J male mice were fed with either a control HF-FD or a HF-MAC diet for 15 weeks. Moreover, an additional group was fed with the HF-MAC diet in combination with an antibiotic cocktail (HF-MAC + AB). Following the 15-week treatment, cognitive behavior was investigated; blood, cecum content, colon, and brain samples were collected to determine metabolic parameters, endotoxin, gut microbiota, colon, and brain pathology. Results We report MACs supplementation prevented HF-FD-induced cognitive impairment in nesting building and temporal order memory tests. MACs prevented gut microbiota dysbiosis, including increasing richness, α-diversity and composition shift, especially in Bacteroidetes and its lower taxa. Furthermore, MACs increased colonic mucus thickness, tight junction protein expression, reduced endotoxemia, and decreased colonic and systemic inflammation. In the hippocampus, MACs suppressed HF-FD-induced neuroglia activation and inflammation, improved insulin IRS-pAKT-pGSK3β-pTau synapse signaling, in addition to the synaptic ultrastructure and associated proteins. Furthermore, MACs’ effects on improving colon–cognitive parameters were eliminated by wide spectrum antibiotic microbiota ablation. Conclusions These results suggest that MACs improve cognitive impairments via the gut microbiota-brain axis induced by the consumption of an HF-FD. Supplemental MACs to combat obesity-related gut and brain dysfunction offer a promising approach to prevent neurodegenerative diseases associated with Westernized dietary patterns and obesity.
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Affiliation(s)
- Hongli Shi
- Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogen Biology and Immunology, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China
| | - Qiao Wang
- Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogen Biology and Immunology, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China
| | - Mingxuan Zheng
- Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogen Biology and Immunology, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China
| | - Shanshan Hao
- Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogen Biology and Immunology, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China
| | - Jeremy S Lum
- Illawarra Health and Medical Research Institute (IHMRI), School of Medicine, University of Wollongong, Wollongong, NSW, 2522, Australia
| | - Xi Chen
- Illawarra Health and Medical Research Institute (IHMRI), School of Medicine, University of Wollongong, Wollongong, NSW, 2522, Australia
| | - Xu-Feng Huang
- Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogen Biology and Immunology, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China.,Illawarra Health and Medical Research Institute (IHMRI), School of Medicine, University of Wollongong, Wollongong, NSW, 2522, Australia
| | - Yinghua Yu
- Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogen Biology and Immunology, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China.
| | - Kuiyang Zheng
- Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogen Biology and Immunology, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China.
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46
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Chen GY, Zhang Q. Simultaneous quantification of free fatty acids and acylcarnitines in plasma samples using dansylhydrazine labeling and liquid chromatography-triple quadrupole mass spectrometry. Anal Bioanal Chem 2020; 412:2841-2849. [PMID: 32078005 DOI: 10.1007/s00216-020-02514-x] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2020] [Revised: 02/04/2020] [Accepted: 02/12/2020] [Indexed: 12/18/2022]
Abstract
Free fatty acid (FFA) and acylcarnitine (AcCar) are key elements of energy metabolism. Dysregulated levels of FFA and AcCar are associated with genetic defects and other metabolic disorders. Due to differences in the physicochemical properties of these two classes of compounds, it is challenging to quantify FFA and AcCar in human plasma using a single method. In this work, we developed a chemical isotope labeling (CIL)-based liquid chromatography-multiple reaction monitoring (LC-MRM) method to simultaneously quantify FFA and AcCar. Dansylhydrazine (DnsHz) was used to label the carboxylic acid moiety on FFA and AcCar. This resulted in the formation of a permanently charged ammonium ion for facile ionization in positive ionization mode and higher hydrophobicity for enhanced retention of short-chain analogs on reversed-phase LC columns and enabled absolute quantification by using heavy labeled DnsHz analogs as internal standards. Labeling conditions including the concentration and freshness of cross-linker, reaction time, and temperature were optimized. This method can successfully quantify all short-, medium- and long-chain FFAs and AcCars with greatly enhanced sensitivity. Using this method, 25 FFAs and 13 AcCars can be absolutely quantified and validated in human plasma samples within 12 min. Simultaneous quantification of FFA and AcCar enabled by this CIL-based LC-MRM method facilitates the investigation of fatty acid metabolism and has potential in clinical applications.
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Affiliation(s)
- Guan-Yuan Chen
- Center for Translational Biomedical Research, University of North Carolina at Greensboro, North Carolina Research Campus, Kannapolis, NC, 28081, USA.,Graduate Institute of Forensic Medicine, National Taiwan University, Taipei, Taiwan
| | - Qibin Zhang
- Center for Translational Biomedical Research, University of North Carolina at Greensboro, North Carolina Research Campus, Kannapolis, NC, 28081, USA. .,Department of Chemistry & Biochemistry, University of North Carolina at Greensboro, Greensboro, NC, 27412, USA.
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47
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Xu L, Hu C, Liu Y, Li S, Vetter W, Yin H, Wang Y. Development of a sensitive and quantitative method for the identification of two major furan fatty acids in human plasma. J Lipid Res 2020; 61:560-569. [PMID: 32029512 DOI: 10.1194/jlr.d119000514] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2019] [Revised: 01/29/2020] [Indexed: 01/28/2023] Open
Abstract
This article focuses on the establishment of an accurate and sensitive quantitation method for the analysis of furan fatty acids. In particular, the sensitivity of GC/MS and UPLC/ESI/MS/MS was compared for the identification and quantification of furan fatty acids. Different methylation methods were tested with respect to GC/MS analysis. Special attention needs to be paid to the methylation of furan fatty acids, as acidic catalysts might lead to the degradation of the furan ring. GC/MS analysis in full-scan mode demonstrated that the limit of quantitation was 10 μM. UPLC/ESI/MS/MS in multiple reaction monitoring mode displayed a higher detection sensitivity than GC/MS. Moreover, the identification of furan fatty acids with charge-reversal derivatization was tested in the positive mode with two widely used pyridinium salts. Significant oxidation was unexpectedly observed using N-(4-aminomethylphenyl) pyridinium as a derivatization agent. The formed 3-acyl-oxymethyl-1-methylpyridinium iodide derivatized by 2-bromo-1-methylpyridinium iodide and 3-carbinol-1-methylpyridinium iodide improved the sensitivity more than 2,000-fold compared with nonderivatization in the negative mode by UPLC/ESI/MS/MS. This charge-reversal derivatization enabled the targeted quantitation of furan fatty acids in human plasma. Thus, it is anticipated that this protocol could greatly contribute to the clarification of pathological mechanisms related to furan fatty acids and their metabolites.
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Affiliation(s)
- Long Xu
- School of Food Science and Engineering, South China University of Technology, Guangzhou, China
| | - Changfeng Hu
- College of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Yongguo Liu
- Beijing Advanced Innovation Centre for Food Nutrition and Human Health, Beijing Key Laboratory of Flavor Chemistry, Beijing Technology and Business University, Beijing, China
| | - Siming Li
- Analytical Applications Center, Analytical Instruments Division, Shimadzu, Guangzhou, China
| | - Walter Vetter
- Institute of Food Chemistry, Department of Food Chemistry (170b), University of Hohenheim, Stuttgart, Germany
| | - Huiyong Yin
- CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
| | - Yonghua Wang
- School of Food Science and Engineering, South China University of Technology, Guangzhou, China
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48
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Du H, Zhao A, Wang Q, Yang X, Ren D. Supplementation of Inulin with Various Degree of Polymerization Ameliorates Liver Injury and Gut Microbiota Dysbiosis in High Fat-Fed Obese Mice. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2020; 68:779-787. [PMID: 31894986 DOI: 10.1021/acs.jafc.9b06571] [Citation(s) in RCA: 62] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
The chain length of fructan determines its different physiological effects. This study is to explore the effects of low-performance inulin [LPI, degree of polymerization (DP) ≤ 9] and high-performance inulin (HPI, DP ≥ 23) on obesity-associated liver injury of high-fat diet (HFD) feeding mice and its underlying mechanism. Eight weeks of supplementation of C57BL/6J mice with HPI, relative to LPI (p < 0.05), caused the more efficient improvement against the HFD-induced liver insulin resistance through activating IRS1/PI3K/Akt pathway and reduced protein expressions of inflammatory factors nuclear factor-kappaB (NF-κB) and interleukin-6 (IL-6) in the liver. HPI exhibited the more positive effects on liver steatosis by inhibiting acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), and sterol regulatory element binding protein 1 (SREBP1) in comparison with LPI (p < 0.05). HPI also increased acetic acid, propionic acid, and butyric acid levels in the colon of HFD-fed mice (p < 0.05). Compared to LPI, HPI feeding of HFD-fed mice led to the more effective decrease in the Firmicutes abundance from 72.1% to 34.5%, but a more significant increase in the Bacteroidetes population from 19.8 to 57.1% at the phyla level, and increased the abundance of Barnesiella, Bacteroides, and Parabacteroides at the genus level (p < 0.05). Depending on DP, HPI exerts the more positive regulation on liver injury and gut microbiota dysfunction than LPI.
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Affiliation(s)
- Haiping Du
- Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, and Shaanxi Key Laboratory for Hazard Factors Assessment in Processing and Storage of Agricultural Products, College of Food Engineering and Nutritional Science , Shaanxi Normal University , Xi'an 710119 , China
| | - Aiqing Zhao
- Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, and Shaanxi Key Laboratory for Hazard Factors Assessment in Processing and Storage of Agricultural Products, College of Food Engineering and Nutritional Science , Shaanxi Normal University , Xi'an 710119 , China
| | - Qi Wang
- Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, and Shaanxi Key Laboratory for Hazard Factors Assessment in Processing and Storage of Agricultural Products, College of Food Engineering and Nutritional Science , Shaanxi Normal University , Xi'an 710119 , China
| | - Xingbin Yang
- Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, and Shaanxi Key Laboratory for Hazard Factors Assessment in Processing and Storage of Agricultural Products, College of Food Engineering and Nutritional Science , Shaanxi Normal University , Xi'an 710119 , China
| | - Daoyuan Ren
- Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, and Shaanxi Key Laboratory for Hazard Factors Assessment in Processing and Storage of Agricultural Products, College of Food Engineering and Nutritional Science , Shaanxi Normal University , Xi'an 710119 , China
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49
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Zhang J, Zhao Y, Ren D, Yang X. Effect of okra fruit powder supplementation on metabolic syndrome and gut microbiota diversity in high fat diet-induced obese mice. Food Res Int 2019; 130:108929. [PMID: 32156377 DOI: 10.1016/j.foodres.2019.108929] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2019] [Revised: 11/29/2019] [Accepted: 12/17/2019] [Indexed: 02/08/2023]
Abstract
This study aimed to explore a novel strategy for dietary okra fruit powder (OFP) consumption on attenuation of non-alcohol fatty liver damage, lipid metabolic disorder and gut microbiota dysbiosis and associated mechanisms in high-fat diet (HFD)-induced obese mice. C57BL/6J mice were fed a normal diet and HFD feeds supplemented with or without OFP (2.5%, 5% and 10%, n = 10) for 12 weeks. The results showed that supplementation of OFP caused strong inhibition on HFD-caused high blood glucose, body weight gain and liver fat accumulation, as well as dyslipidemia involved in a dose-dependent modulation of hepatic FAS and CD36 expressions of obese mice. The hepatic LXR-α energy metabolism and PPAR-α pathway were also doubly activated by OFP to alleviate lipogenesis, obesity and metabolic syndrome. Malonaldehyde production was effectively antagonized, and glutathione peroxidase and superoxide dismutase activities were elevated by OFP supplementation in HFD-fed mice. OFP also significantly improved colonic SCFAs (acetic acid, propionic acid and butyrate acid) formation, especially for butyrate production via increasing the proportion of selected butyrate-producing bacteria. OFP also dramatically modified the gut microbial species at the family level with suppressing an increase in Proteobacteria, Actinobacteria and F/B ratio, and the decrease in Bacteroidetes caused by HFD. These findings support that dietary OFP consumption is a novel strategy to prevent obesity, metabolic syndrome and gut microbiota imbalance.
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Affiliation(s)
- Jin Zhang
- Key Laboratory of Ministry of Education for Medicinal Resource and Natural Pharmaceutical Chemistry, College of Life Sciences, Shaanxi Normal University, Xi'an 710062, China
| | - Yan Zhao
- Key Laboratory of Ministry of Education for Medicinal Resource and Natural Pharmaceutical Chemistry, College of Life Sciences, Shaanxi Normal University, Xi'an 710062, China.
| | - Daoyuan Ren
- Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, and Shaanxi Key Laboratory for Hazard Factors Assessment in Processing and Storage of Agricultural Products, College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an 710062, China
| | - Xingbin Yang
- Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, and Shaanxi Key Laboratory for Hazard Factors Assessment in Processing and Storage of Agricultural Products, College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an 710062, China.
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50
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Franco-Martínez L, Martínez-Subiela S, Cerón JJ, Tecles F, Eckersall PD, Oravcova K, Tvarijonaviciute A. Biomarkers of health and welfare: A One Health perspective from the laboratory side. Res Vet Sci 2019; 128:299-307. [PMID: 31869596 DOI: 10.1016/j.rvsc.2019.12.012] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2019] [Revised: 11/22/2019] [Accepted: 12/10/2019] [Indexed: 10/25/2022]
Abstract
A biomarker is any measurement reflecting an interaction between a biological system and a potential hazard, which may be chemical, physical, or biological. The One World, One Health concept established that human and animal health and the environmental state are highly interconnected, sharing common aspects that can be applied globally in these three components. In this paper, we review how the concept of One Health can be applied to biomarkers of health and welfare, with a special focus on five points that can be applied to any biomarker when it is expected to be used to evaluate the human, animal or environmental health. Three of these points are: (1) the different biomarkers that can be used, (2) the different sample types where the biomarkers can be analysed, and (3) the main methods that can be used for their measurement. In addition, we will evaluate two key points needed for adequate use of a biomarker in any situation: (4) a proper analytical validation in the sample that it is going to be used, and (5) a correct selection of the biomarker. It is expected that this knowledge will help to have a broader idea about the use of biomarkers of health and welfare and also will contribute to a better and more accurate use of these biomarkers having in mind their One Health perspective.
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Affiliation(s)
- Lorena Franco-Martínez
- Interdisciplinary Laboratory of Clinical Analysis (Interlab-UMU), Veterinary School, Campus of Excellence Mare Nostrum, University of Murcia, Espinardo, 30100 Murcia, Spain.
| | - Silvia Martínez-Subiela
- Interdisciplinary Laboratory of Clinical Analysis (Interlab-UMU), Veterinary School, Campus of Excellence Mare Nostrum, University of Murcia, Espinardo, 30100 Murcia, Spain.
| | - José Joaquín Cerón
- Interdisciplinary Laboratory of Clinical Analysis (Interlab-UMU), Veterinary School, Campus of Excellence Mare Nostrum, University of Murcia, Espinardo, 30100 Murcia, Spain.
| | - Fernando Tecles
- Interdisciplinary Laboratory of Clinical Analysis (Interlab-UMU), Veterinary School, Campus of Excellence Mare Nostrum, University of Murcia, Espinardo, 30100 Murcia, Spain.
| | - Peter David Eckersall
- Institute of Biodiversity, Animal Health and Comparative Medicine, University of Glasgow, Bearsden Rd, Glasgow G61 1QH, UK.
| | - Katarina Oravcova
- Institute of Biodiversity, Animal Health and Comparative Medicine, University of Glasgow, Bearsden Rd, Glasgow G61 1QH, UK.
| | - Asta Tvarijonaviciute
- Interdisciplinary Laboratory of Clinical Analysis (Interlab-UMU), Veterinary School, Campus of Excellence Mare Nostrum, University of Murcia, Espinardo, 30100 Murcia, Spain.
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