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Li Y, Zhang Z, Han Q, Liu G, Yin Y, Yin J. Lactobacillus johnsonii-derived leucic acid promotes fatty acid absorption and deposition by targeting CD36. SCIENCE CHINA. LIFE SCIENCES 2025:10.1007/s11427-024-2794-4. [PMID: 40120026 DOI: 10.1007/s11427-024-2794-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Accepted: 11/25/2024] [Indexed: 03/25/2025]
Abstract
Lactobacillus johnsonii is a microbial biomarker associated with lipid deposition, but the mechanism by which it accelerates fatty acid absorption and deposition remains unclear. In this study, we isolated a strain of L. johnsonii MS0621 from the feces of Ningxiang pigs, an obese animal model, and evaluated its probiotic properties with high resistance to temperature and intestinal fluids. Colonization by L. johnsonii MS0621 increased the abundance of gut Lactobacillus in lean DLY pigs, concomitant with increases in fatty acid absorption in the intestine and lipid depositions in the fat and muscle tissues. The lipid absorption-promoting effect was further detected in IPEC-J2 cells treated with live L. johnsonii MS0621 and the bacteria-free supernatants, as evidenced by high triglyceride synthesis and the expression of CD36, a key lipid transporter. Metabolomics analysis showed that (R)-leucic acid is a potential metabolite targeting CD36 expression to guarantee lipid absorption and deposition. The mechanism might involve direct interaction with CD36, as molecular docking and inhibition of CD36 blocked L. johnsonii MS0621 or derived metabolite-mediated lipid absorption. In conclusion, we uncovered an important role of L. johnsonii MS0621 derived (R)-leucic acid in regulating the absorption and deposition of intestinal fatty acids via regulation of CD36 expression.
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Affiliation(s)
- Yunxia Li
- College of Animal Science and Technology, Hunan Agriculture University, Changsha, 410128, China
- Yuelushan Laboratory, Changsha, 410128, China
| | - Zhiming Zhang
- College of Animal Science and Technology, Hunan Agriculture University, Changsha, 410128, China
- Yuelushan Laboratory, Changsha, 410128, China
| | - Qi Han
- College of Animal Science and Technology, Hunan Agriculture University, Changsha, 410128, China
- Yuelushan Laboratory, Changsha, 410128, China
| | - Gang Liu
- Yuelushan Laboratory, Changsha, 410128, China
- College of Bioscience and Biotechnology, Hunan Agriculture University, Changsha, 410128, China
| | - Yulong Yin
- Yuelushan Laboratory, Changsha, 410128, China
- Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, 410125, China
| | - Jie Yin
- College of Animal Science and Technology, Hunan Agriculture University, Changsha, 410128, China.
- Yuelushan Laboratory, Changsha, 410128, China.
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2
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Yuan Y, Chi B, Fan J, Wang Y, Luo G, Gao X. Enhancing the Accuracy of Identification and Relative Quantification of Unsaturated Fatty Acids in Serum via a Stable Isotope-Labeled Double Derivatization Strategy. Anal Chem 2025; 97:5126-5137. [PMID: 40019293 DOI: 10.1021/acs.analchem.4c06375] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/01/2025]
Abstract
Accurate identification and quantification of fatty acids are critical for investigating their biological function in disease models. Although several derivatization methods have been proposed for identifying the positions of C═C bonds in unsaturated fatty acids, poor ionization efficiency of the carboxyl group leads to lower intensity of molecular ion peaks, making their identification difficult and interfering with the accuracy of quantification based on peak areas of characteristic ion pairs. In this study, a strategy of stable isotope-labeled carboxyl derivatization combined with C═C derivatization was employed for simultaneously the identification and quantification of fatty acids using d0/d9-5-amino-N,N,N-trimethylpentane-1-ammonium iodide (d0/d9-ATPAI) to label the carboxyl group and m-chloroperoxybenzoic acid to label C═C bonds. The stable isotope-labeled quaternary amine groups in the novel carboxyl derivatization reagent d0/d9-ATPAI can enhance the accuracy of the recognition of characteristic ion pairs to facilitate the structural elucidation of various fatty acids. The heavy isotope-labeled fatty acids can be served as internal standards to achieve accurate relative quantification of the C═C position isomers of individual unsaturated fatty acids among samples based on the peak area ratio of the characteristic ion pairs. Unsaturated fatty acid C═C positional isomers were quantified using aldehyde or alkenyl diagnostic ions. In addition, saturated fatty acids were quantified using the m/z 86.09679 cyclamine characteristic ion. This approach enhanced the detection sensitivity of fatty acids by 60,000 times, allowing for the characterization of 70 fatty acids in rat serum, including 26 unsaturated fatty acid C═C positional isomers. Pseudotargeted metabolomics analysis of serum fatty acids revealed alterations in the fatty acid metabolic pathway during diabetic cognitive dysfunction. Overall, the proposed method, with high sensitivity and wide coverage, could provide accurate identification and relative quantification of various fatty acids in complex matrices.
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Affiliation(s)
- Yunxia Yuan
- Department of Chinese Medicine Analysis, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China
| | - Bingqing Chi
- Department of Chinese Medicine Analysis, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China
| | - Jiajia Fan
- Department of Chinese Medicine Analysis, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China
| | - Ying Wang
- Department of Chinese Medicine Analysis, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China
| | - Gan Luo
- Department of Chinese Medicine Analysis, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China
| | - Xiaoyan Gao
- Department of Chinese Medicine Analysis, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China
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3
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Jiang Q, Zhang D, Hu N, Ma Y, Jin H, Zhao Y, Zhang M, Li B, Huang Z, Yuan B, Zhu Y, Tian J, Miao X. Environmental Chemical-Induced Cardiometabolic Disorders: Combined Epidemiological and Experimental Evidence. ENVIRONMENTAL SCIENCE & TECHNOLOGY 2025; 59:3853-3868. [PMID: 39977603 DOI: 10.1021/acs.est.4c09728] [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: 02/22/2025]
Abstract
Screening environmental pollutants that are harmful to the cardiometabolic status and understanding their key toxic pathways are crucial for effective clinical intervention. Based on exposure data of 46 chemicals in a nationally representative 13,286 people, logistic regression and mixture modeling were used to preliminarily identify environmental pollutants with significant impacts on 12 indicators for cardiometabolic disorders. A total of 15 chemicals were found to be associated with the integrated latent class, among which four chemicals (perfluorononanoic acid [PFNA], perfluorooctanoic acid [PFOA], thiocyanate, and thallium) also contributed significantly to the mixture effect. We constructed the adverse outcome pathways (AOPs) for nine significant toxicants in both models of individual chemicals and the mixture for each cardiometabolic disorder. Notably, fluoroalkyl substances affect multiple aspects of hyperlipidemia by activating PPARα. We performed molecular docking and in vitro experiments to verify and supplement the toxicological mechanism of PFNA. Through binding to PPARα, PFNA increased the levels of downstream molecules including CD36 (fatty acid transfer), ACSL1 (fatty acid activation), and CPT1a (intracellular transfer for β-oxidation) and ultimately promoted the accumulation of triglycerides and lipid droplets in HepG2 cells. These markers, together with key events for other metabolic phenotypes, may be potential targets for scientific research or clinical treatment.
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Affiliation(s)
- Qi Jiang
- Department of Epidemiology and Biostatistics, School of Public Health, Research Center of Public Health, Renmin Hospital of Wuhan University, Department of Gastrointestinal Oncology, Zhongnan Hospital of Wuhan University, TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, Hubei 430071, China
| | - Donghui Zhang
- Department of Epidemiology and Biostatistics, School of Public Health, Research Center of Public Health, Renmin Hospital of Wuhan University, Department of Gastrointestinal Oncology, Zhongnan Hospital of Wuhan University, TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, Hubei 430071, China
| | - Naifan Hu
- Department of Epidemiology and Biostatistics, School of Public Health, Research Center of Public Health, Renmin Hospital of Wuhan University, Department of Gastrointestinal Oncology, Zhongnan Hospital of Wuhan University, TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, Hubei 430071, China
| | - Yunfei Ma
- Department of Epidemiology and Biostatistics, School of Public Health, Wuhan University, Wuhan 430071, China
| | - Huibin Jin
- Department of Epidemiology and Biostatistics, School of Public Health, Wuhan University, Wuhan 430071, China
| | - Yunhao Zhao
- Department of Epidemiology and Biostatistics, School of Public Health, Wuhan University, Wuhan 430071, China
| | - Ming Zhang
- Department of Epidemiology and Biostatistics, School of Public Health, Wuhan University, Wuhan 430071, China
| | - Bin Li
- Department of Epidemiology and Biostatistics, School of Public Health, Wuhan University, Wuhan 430071, China
| | - Zhenzhen Huang
- Department of Occupational and Environmental Health, School of Public Health, Wuhan University, Wuhan 430071, China
| | - Bifeng Yuan
- Department of Occupational and Environmental Health, School of Public Health, Wuhan University, Wuhan 430071, China
| | - Ying Zhu
- Department of Epidemiology and Biostatistics, School of Public Health, Research Center of Public Health, Renmin Hospital of Wuhan University, Department of Gastrointestinal Oncology, Zhongnan Hospital of Wuhan University, TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, Hubei 430071, China
| | - Jianbo Tian
- Department of Epidemiology and Biostatistics, School of Public Health, Research Center of Public Health, Renmin Hospital of Wuhan University, Department of Gastrointestinal Oncology, Zhongnan Hospital of Wuhan University, TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, Hubei 430071, China
| | - Xiaoping Miao
- Department of Epidemiology and Biostatistics, School of Public Health, Research Center of Public Health, Renmin Hospital of Wuhan University, Department of Gastrointestinal Oncology, Zhongnan Hospital of Wuhan University, TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, Hubei 430071, China
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Fox EA, Serlin HK. Gaps in our understanding of how vagal afferents to the small intestinal mucosa detect luminal stimuli. Am J Physiol Regul Integr Comp Physiol 2024; 327:R173-R187. [PMID: 38860288 DOI: 10.1152/ajpregu.00252.2023] [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: 11/13/2023] [Revised: 05/10/2024] [Accepted: 05/24/2024] [Indexed: 06/12/2024]
Abstract
Vagal afferents to the gastrointestinal tract are crucial for the regulation of food intake, signaling negative feedback that contributes to satiation and positive feedback that produces appetition and reward. Vagal afferents to the small intestinal mucosa contribute to this regulation by sensing luminal stimuli and reporting this information to the brain. These afferents respond to mechanical, chemical, thermal, pH, and osmolar stimuli, as well as to bacterial products and immunogens. Surprisingly, little is known about how these stimuli are transduced by vagal mucosal afferents or how their transduction is organized among these afferents' terminals. Furthermore, the effects of stimulus concentration ranges or physiological stimuli on vagal activity have not been examined for some of these stimuli. Also, detection of luminal stimuli has rarely been examined in rodents, which are most frequently used for studying small intestinal innervation. Here we review what is known about stimulus detection by vagal mucosal afferents and illustrate the complexity of this detection using nutrients as an exemplar. The accepted model proposes that nutrients bind to taste receptors on enteroendocrine cells (EECs), which excite them, causing the release of hormones that stimulate vagal mucosal afferents. However, evidence reviewed here suggests that although this model accounts for many aspects of vagal signaling about nutrients, it cannot account for all aspects. A major goal of this review is therefore to evaluate what is known about nutrient absorption and detection and, based on this evaluation, identify candidate mucosal cells and structures that could cooperate with EECs and vagal mucosal afferents in stimulus detection.
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Affiliation(s)
- Edward A Fox
- Behavioral Neurogenetics Laboratory, Department of Psychological Sciences, Purdue University, West Lafayette, Indiana, United States
| | - Hannah K Serlin
- Behavioral Neurogenetics Laboratory, Department of Psychological Sciences, Purdue University, West Lafayette, Indiana, United States
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Sun J, Xie F, Wang J, Luo J, Chen T, Jiang Q, Xi Q, Liu GE, Zhang Y. Integrated meta-omics reveals the regulatory landscape involved in lipid metabolism between pig breeds. MICROBIOME 2024; 12:33. [PMID: 38374121 PMCID: PMC10877772 DOI: 10.1186/s40168-023-01743-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/17/2023] [Accepted: 12/19/2023] [Indexed: 02/21/2024]
Abstract
BACKGROUND Domesticated pigs serve as an ideal animal model for biomedical research and also provide the majority of meat for human consumption in China. Porcine intramuscular fat content associates with human health and diseases and is essential in pork quality. The molecular mechanisms controlling lipid metabolism and intramuscular fat accretion across tissues in pigs, and how these changes in response to pig breeds, remain largely unknown. RESULTS We surveyed the tissue-resident cell types of the porcine jejunum, colon, liver, and longissimus dorsi muscle between Lantang and Landrace breeds by single-cell RNA sequencing. Combining lipidomics and metagenomics approaches, we also characterized gene signatures and determined key discriminating markers of lipid digestibility, absorption, conversion, and deposition across tissues in two pig breeds. In Landrace, lean-meat swine mainly exhibited breed-specific advantages in lipid absorption and oxidation for energy supply in small and large intestinal epitheliums, nascent high-density lipoprotein synthesis for reverse cholesterol transport in enterocytes and hepatocytes, bile acid formation, and secretion for fat emulsification in hepatocytes, as well as intestinal-microbiota gene expression involved in lipid accumulation product. In Lantang, obese-meat swine showed a higher synthesis capacity of chylomicrons responsible for high serum triacylglycerol levels in small intestinal epitheliums, the predominant characteristics of lipid absorption in muscle tissue, and greater intramuscular adipcytogenesis potentials from muscular fibro-adipogenic progenitor subpopulation. CONCLUSIONS The findings enhanced our understanding of the cellular biology of lipid metabolism and opened new avenues to improve animal production and human diseases. Video Abstract.
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Affiliation(s)
- Jiajie Sun
- Guangdong Provincial Key Laboratory of Animal Nutrition Control, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, Guangdong, 510642, China
| | - Fang Xie
- Guangdong Provincial Key Laboratory of Animal Nutrition Control, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, Guangdong, 510642, China
| | - Jing Wang
- Institute of Animal Husbandry and Veterinary Medicine, Henan Academy of Agricultural Sciences, Zhengzhou, 450002, China
| | - Junyi Luo
- Guangdong Provincial Key Laboratory of Animal Nutrition Control, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, Guangdong, 510642, China
| | - Ting Chen
- Guangdong Provincial Key Laboratory of Animal Nutrition Control, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, Guangdong, 510642, China
| | - Qingyan Jiang
- Guangdong Provincial Key Laboratory of Animal Nutrition Control, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, Guangdong, 510642, China
| | - Qianyun Xi
- Guangdong Provincial Key Laboratory of Animal Nutrition Control, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, Guangdong, 510642, China.
| | - George E Liu
- Animal Genomics and Improvement Laboratory, USDA-ARS, BARC-East, Beltsville, MD, 20705, USA.
| | - Yongliang Zhang
- Guangdong Provincial Key Laboratory of Animal Nutrition Control, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, Guangdong, 510642, China.
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Zhong H, Yu W, Wang M, Lin B, Sun X, Zheng N, Wang J, Zhao S. Sodium butyrate promotes gastrointestinal development of preweaning bull calves via inhibiting inflammation, balancing nutrient metabolism, and optimizing microbial community functions. ANIMAL NUTRITION (ZHONGGUO XU MU SHOU YI XUE HUI) 2023; 14:88-100. [PMID: 37388163 PMCID: PMC10300058 DOI: 10.1016/j.aninu.2023.04.004] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/09/2022] [Revised: 03/26/2023] [Accepted: 04/19/2023] [Indexed: 07/01/2023]
Abstract
Butyrate promotes the growth and gastrointestinal development of calves. But, the mechanisms behind its effects on signaling pathways of the gastrointestinal tract and rumen microbiome is unclear. This study aimed to reveal transcriptomic pathways of gastrointestinal epithelium and microbial community in response to butyrate supplementation in calves fed a high fiber starter. Fourteen Holstein bull calves (39.9 ± 3.7 kg, 14 d of age) were assigned to 2 groups (sodium butyrate group, SB; control group, Ctrl). The SB group received 0.5% SB supplementation. At d 51, the calves were slaughtered to obtain samples for analysis of the transcriptome of the rumen and jejunum epithelium as well as ruminal microbial metagenome. Sodium butyrate supplementation resulted in a higher performance in average daily gain and development of jejunum and rumen papillae. In both the rumen and jejunum epithelium, SB down-regulated pathways related to inflammation including NF-κB (PPKCB, CXCL8, CXCL12), interleukin-17 (IL17A, IL17B, MMP9), and chemokine (CXCL12, CCL4, CCL8) and up-regulated immune pathways including the intestinal immune network for immunoglobulin A (IgA) production (CD28). Meanwhile, in the jejunum epithelium, SB regulated pathways related to nutritional metabolism including nitrogen metabolism (CA1, CA2, CA3), synthesis and degradation of ketone bodies (HMGCS2, BDH1, LOC100295719), fat digestion and absorption (PLA2G2F, APOA1, APOA4), and the PPAR signaling pathway (FABP4, FABP6, CYP4A11). The metagenome showed that SB greatly increased the relative abundance of Bacillus subtilis and Eubacterium limosum, activated ruminal microbial carbohydrate metabolism pathways and increased the abundance of carbohydrate hydrolysis enzymes. In conclusion, butyrate exhibited promoting effects on growth and gastrointestinal development by inhibiting inflammation, enhancing immunity and energy harvesting, and activating microbial carbohydrate metabolism. These findings provide new insights into the potential mechanisms behind the beneficial effects of butyrate in calf nutrition.
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Affiliation(s)
- Huiyue Zhong
- State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, China
| | - Wenjing Yu
- Department of Animal Science and Technology, Guangxi University, Nanning, 530005, China
| | - Min Wang
- Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, 410125, China
| | - Bo Lin
- Department of Animal Science and Technology, Guangxi University, Nanning, 530005, China
| | - Xuezhao Sun
- Jilin Inter-regional Cooperation Centre for the Scientific and Technological Innovation of Ruminant Precision Nutrition and Smart and Ecological Farming, Jilin Agricultural Science and Technology University, Jilin, 132109, China
- Grasslands Research Centre, AgResearch Limited, Palmerston North, New Zealand
| | - Nan Zheng
- State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, China
| | - Jiaqi Wang
- State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, China
| | - Shengguo Zhao
- State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, China
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Yang TM, Miao M, Yu WQ, Wang X, Xia FJ, Li YJ, Guo SD. Targeting macrophages in atherosclerosis using nanocarriers loaded with liver X receptor agonists: A narrow review. Front Mol Biosci 2023; 10:1147699. [PMID: 36936982 PMCID: PMC10018149 DOI: 10.3389/fmolb.2023.1147699] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2023] [Accepted: 02/20/2023] [Indexed: 03/06/2023] Open
Abstract
Macrophages are involved in the whole process of atherosclerosis, which is characterized by accumulation of lipid and inflammation. Presently, clinically used lipid-lowering drugs cannot completely retard the progress of atherosclerosis. Liver X receptor (LXR) plays a key role in regulation of lipid metabolism and inflammation. Accumulating evidence have demonstrated that synthetic LXR agonists can significantly retard the development of atherosclerosis. However, these agonists induce sever hypertriglyceridemia and liver steatosis. These side effects have greatly limited their potential application for therapy of atherosclerosis. The rapid development of drug delivery system makes it possible to delivery interested drugs to special organs or cells using nanocarriers. Macrophages express various receptors which can recognize and ingest specially modified nanocarriers loaded with LXR agonists. In the past decades, a great progress has been made in this field. These macrophage-targeted nanocarriers loaded with LXR agonists are found to decrease atherosclerosis by reducing cholesterol accumulation and inflammatory reactions. Of important, these nanocarriers can alleviate side effects of LXR agonists. In this article, we briefly review the roles of macrophages in atherosclerosis, mechanisms of action of LXR agonists, and focus on the advances of macrophage-targeted nanocarriers loaded with LXR agonists. This work may promote the potential clinical application of these nanocarriers.
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Affiliation(s)
| | | | | | | | | | - Yan-Jie Li
- *Correspondence: Yan-Jie Li, ; Shou-Dong Guo,
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Yu H, Bai S, Hao Y, Guan Y. Fatty acids role in multiple sclerosis as "metabokines". J Neuroinflammation 2022; 19:157. [PMID: 35715809 PMCID: PMC9205055 DOI: 10.1186/s12974-022-02502-1] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Accepted: 06/01/2022] [Indexed: 12/21/2022] Open
Abstract
Multiple sclerosis (MS), as an autoimmune neurological disease with both genetic and environmental contribution, still lacks effective treatment options among progressive patients, highlighting the need to re-evaluate disease innate properties in search for novel therapeutic targets. Fatty acids (FA) and MS bear an interesting intimate connection. FA and FA metabolism are highly associated with autoimmunity, as the diet-derived circulatory and tissue-resident FAs level and composition can modulate immune cells polarization, differentiation and function, suggesting their broad regulatory role as “metabokines”. In addition, FAs are indeed protective factors for blood–brain barrier integrity, crucial contributors of central nervous system (CNS) chronic inflammation and progressive degeneration, as well as important materials for remyelination. The remaining area of ambiguity requires further exploration into this arena to validate the existed phenomenon, develop novel therapies, and confirm the safety and efficacy of therapeutic intervention targeting FA metabolism.
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Affiliation(s)
- Haojun Yu
- Department of Neurology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, 160 Pujian Road, Pudong, Shanghai, 200127, China
| | - Shuwei Bai
- Department of Neurology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, 160 Pujian Road, Pudong, Shanghai, 200127, China
| | - Yong Hao
- Department of Neurology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, 160 Pujian Road, Pudong, Shanghai, 200127, China.
| | - Yangtai Guan
- Department of Neurology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, 160 Pujian Road, Pudong, Shanghai, 200127, China.
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Gong Y, Liu Y, Wang T, Li Z, Gao L, Chen H, Shu Y, Li Y, Xu H, Zhou Z, Dai L. Age-Associated Proteomic Signatures and Potential Clinically Actionable Targets of Colorectal Cancer. Mol Cell Proteomics 2021; 20:100115. [PMID: 34129943 PMCID: PMC8441843 DOI: 10.1016/j.mcpro.2021.100115] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Revised: 05/04/2021] [Accepted: 06/08/2021] [Indexed: 02/06/2023] Open
Abstract
The occurrence and prevalence of colorectal cancer (CRC) is closely associated with age. More than 90% of patients with CRC are diagnosed after 50 years of age. However, CRC incidence of young individuals has been increasing since 1990s, whereas the overall CRC frequency is declining. Distinct overall survival rates between young and aged patients with CRC have been established. Tremendous efforts have been made to clarify the underlying mechanisms of age-dependent clinical differences, but it still remains elusive. Here, we performed proteomic profiling of 50 patients with CRC and revealed proteomic signatures of CRC across age groups. Gene set enrichment analysis showed that distinct age-dependent clinical outcomes might mainly attribute to varied MYC targets V1/V2, E2F targets and G2M checkpoint gene sets, which were associated with cancer cell proliferation, cell apoptosis, tumor growth, and tumor metastasis. Multiple linear regression analysis revealed a large number of functional proteins, such as NOP2, CSE1L, NHP2, NOC2L and CDK1, with adjusted expression significantly correlated with age (p < 0.05). Among them, NHP2 is a core component of the telomerase complex associated with age. High NHP2 expression predicted poor overall survival, with a more significant correlation in aged patients with CRC. Knockdown of NHP2 significantly suppressed cancer cell proliferation. In addition, we revealed some age-related potential clinically actionable targets, such as PSEN1, TSPO, and CDK1, which might be more suitable for patients with late-onset CRC. Collectively, this study identifies age-associated proteomic signatures and potential therapeutic targets of CRC and may help make a precise decision on CRC treatment.
The proteomic signatures of early-onset CRC are disclosed. Alterations of some proteins between cancerous and normal tissues are age-correlated. NHP2, overexpressed in tumors especially in aged patients, predicts poor prognosis. Potential age-dependent druggable targets and their inhibitors are summarized.
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Affiliation(s)
- Yanqiu Gong
- Department of Gastrointestinal Surgery, National Clinical Research Center for Geriatrics and Department of General Practice, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu, China
| | - Yu Liu
- Department of Gastrointestinal Surgery, National Clinical Research Center for Geriatrics and Department of General Practice, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu, China
| | - Tian Wang
- Life Science Mass Spectrometry Service Department, Thermo Fisher Scientific (China) Co, Chengdu, China
| | - Zhigui Li
- Department of Gastrointestinal Surgery, National Clinical Research Center for Geriatrics and Department of General Practice, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu, China
| | - Li Gao
- Department of Gastrointestinal Surgery, National Clinical Research Center for Geriatrics and Department of General Practice, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu, China
| | - Haining Chen
- Department of Gastrointestinal Surgery, National Clinical Research Center for Geriatrics and Department of General Practice, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu, China
| | - Yang Shu
- Department of Gastrointestinal Surgery, National Clinical Research Center for Geriatrics and Department of General Practice, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu, China
| | - Yuan Li
- Department of Gastrointestinal Surgery, National Clinical Research Center for Geriatrics and Department of General Practice, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu, China
| | - Heng Xu
- Department of Gastrointestinal Surgery, National Clinical Research Center for Geriatrics and Department of General Practice, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu, China
| | - Zongguang Zhou
- Department of Gastrointestinal Surgery, National Clinical Research Center for Geriatrics and Department of General Practice, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu, China.
| | - Lunzhi Dai
- Department of Gastrointestinal Surgery, National Clinical Research Center for Geriatrics and Department of General Practice, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu, China.
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10
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Koriem KMM. Lipidome is lipids regulator in gastrointestinal tract and it is a life collar in COVID-19: A review. World J Gastroenterol 2021; 27:37-54. [PMID: 33505149 PMCID: PMC7789067 DOI: 10.3748/wjg.v27.i1.37] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Revised: 12/02/2020] [Accepted: 12/17/2020] [Indexed: 02/06/2023] Open
Abstract
The term lipidome is mentioned to the total amount of the lipids inside the biological cells. The lipid enters the human gastrointestinal tract through external source and internal source. The absorption pathway of lipids in the gastrointestinal tract has many ways; the 1st way, the lipid molecules are digested in the lumen before go through the enterocytes, digested products are re-esterified into complex lipid molecules. The 2nd way, the intracellular lipids are accumulated into lipoproteins (chylomicrons) which transport lipids throughout the whole body. The lipids are re-synthesis again inside the human body where the gastrointestinal lipids are: (1) Transferred into the endoplasmic reticulum; (2) Collected as lipoproteins such as chylomicrons; or (3) Stored as lipid droplets in the cytosol. The lipids play an important role in many stages of the viral replication cycle. The specific lipid change occurs during viral infection in advanced viral replication cycle. There are 47 lipids within 11 lipid classes were significantly disturbed after viral infection. The virus connects with blood-borne lipoproteins and apolipoprotein E to change viral infectivity. The viral interest is cholesterol- and lipid raft-dependent molecules. In conclusion, lipidome is important in gastrointestinal fat absorption and coronavirus disease 2019 (COVID-19) infection so lipidome is basic in gut metabolism and in COVID-19 infection success.
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