The prevalence of obesity has increased worldwide in recent decades. Genetic factors are now known to play a substantial role in the predisposition to obesity and may contribute up to 70% of the risk for obesity. Technological advancements during the last decades have allowed the identification of many hundreds of genetic markers associated with obesity. However, the transformation of current genetic variant-obesity associations into biological knowledge has been proven challenging. Genomics and proteomics are complementary fields, as proteomics extends functional analyses. Integrating genomic and proteomic data can help to bridge a gap in knowledge regarding genetic variant-obesity associations and to identify new drug targets for the treatment of obesity. We provide an overview of the published papers on the integrated analysis of proteomic and genomic data in obesity and summarize four mainstream strategies: overlap, colocalization, Mendelian randomization, and proteome-wide association studies. The integrated analyses identified many obesity-associated proteins, such as leptin, follistatin, and adenylate cyclase 3. Despite great progress, integrative studies focusing on obesity are still limited. There is an increased demand for large prospective cohort studies to identify and validate findings, and further apply these findings to the prevention, intervention, and treatment of obesity. In addition, we also discuss several other potential integration methods.
Humans ; Proteome/metabolism* ; Proteomics ; Prospective Studies ; Obesity/genetics* ; Genomics ; Genome-Wide Association Study

The effects of Jingui Shenqi Pills(Jingui) and Liuwei Dihuang Pills(Liuwei) which respectively tonify kidney Yang and kidney Yin on brain function have attracted great attention, while the differences of protein expression regulated by Jingui and Liuwei remain to be studied. This study explored the difference of protein expression profiles in the hippocampi of mice orally administrated with the two drugs for 7 days. The protein expression was quantified using LC-MS/MS. The results showed that among the 5 860 proteins tested, 151, 282 and 75 proteins responded to Jingui alone, Liuwei alone, and both drugs, respectively. The ratio of up-regulated proteins to down-regulated proteins was 1.627 in Jingui group while only 0.56 in Liuwei group. The proteins up-regulated by Jingui were mainly involved in membrane transport, synaptic vesicle cycle, serotonergic synapse, dopaminergic synapse and so on, suggesting that Jingui may play a role in promoting the transport of neurotransmitter in the nervous system. The proteins down-regulated by Liuwei were mainly involved in membrane transport, synapse, ion transport(potassium and sodium transport), neurotransmitter transport, innate and acquired immune responses, complement activation, inflammatory response, etc. In particular, Liuwei showed obvious down-regulation effect on the members of solute carrier(SLC) superfamily, which suggested that Liuwei had potential inhibitory effect on membrane excitation and transport. Finally, consistent results were obtained in the normal mouse and the mouse model with corticosterone-induced depressive-like behavior. This study provides an experimental basis for understanding the effect of Jingui and Liuwei on brain function from protein network.
Animals ; Chromatography, Liquid ; Drugs, Chinese Herbal/pharmacology* ; Hippocampus/metabolism* ; Mice ; Proteome/metabolism* ; Proteomics ; Tandem Mass Spectrometry

The systematic and in-depth study of phosphoproteome rely on highly reproducible and specific phosphopeptide enrichment methods. At present, a variety of enrichment methods have been developed based on different principles, and these methods often display different selectivity and specificity. It is therefore very important to select the most suitable enrichment method according to different research purposes. This review summarized the phosphopeptide enrichment based on affinity chromatography, immunoprecipitation, chemical derivatization, chromatography and other newly developed methods. The advantages and disadvantages of these methods, as well as the related optimization and improvement strategies, were discussed in detail. In addition, we also briefly summarized the progress of the combination of phosphopeptide enrichment and fractionation methods developed in recent years.
Phosphopeptides/metabolism* ; Proteomics/methods* ; Titanium/chemistry* ; Chromatography, Affinity ; Proteome ; Phosphorylation

Methotrexate (MTX) is a widely used immunosuppressive drug. Large-dose of MTX is used for the treatment of cancer while low-dose is used for the treatment of rheumatoid arthritis (RA). This study aimed to explore the effect of MTX on the urinary proteome of rats. MTX was given to rats orally to construct an MTX intragastric administration rat model. The urine of the rats were collected within 10 hours after giving MTX, and the urine proteins of the rats were analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS). A total of 31 differential proteins were identified, of which 7 proteins were related to the effect MTX and the symptom of RA. The biological processes of some rats reflected the effect of MTX on the body's glutathione metabolism and the JAK/STAT signaling pathway, which indicated that urine proteins have the ability to reflect the effects of MTX on the body of rats. The spectrum of the differential proteins of each single rat showed that different individuals respond to the drug quite differently.
Rats ; Animals ; Methotrexate/metabolism* ; Proteome ; Chromatography, Liquid/methods* ; Tandem Mass Spectrometry/methods* ; Arthritis, Rheumatoid/drug therapy*

Objective To obtain the proteome and acetylome profiles of livers in mice during normal aging.Methods We applied tandem mass tag labeling and liquid chromatography tandem mass spectrometry and achieved proteome and acetylome data in C57BL/6J male mice aged 2 and 18 months under physiological conditions.Results A total of 4712 proteins were quantified by proteome profiling,and 4818 acetylated sites in 1367 proteins by acetylome profiling.The proteome and acetylome revealed moderate differences in the livers of young and old mice.There were 195 differentially expressed proteins in the proteome and 113 differentially expressed acetylated sites corresponding to 76 proteins in the acetylome.Functional enrichment analysis for the proteome showed that aging-associated upregulated proteins were mainly involved in fatty acid metabolism,epoxygenase P450 pathway,drug catabolic process,organic hydroxy compound metabolic process,and arachidonic acid metabolic process,while the downregulated proteins were related to regulation of gene silencing,nucleosome assembly,protein heterotetramerization,response to interferon,protein-DNA complex assembly and other processes.For the acetylome,the proteins with aging-associated upregulated acetylated sites mainly participated in cofactor metabolism,small molecule catabolic process,ribose phosphate metabolic process,ribonucleotide metabolic process,and purine-containing compound metabolic process,while the proteins with downregulated acetylated sites were associated with sulfur compound metabolic process,response to unfolded protein,and amino acid metabolic process.Conclusion We profiled the proteome and acetylome of livers in mice during normal aging and generated datasets for further research on aging.
Acetylation ; Aging ; Animals ; Liver ; Lysine/metabolism* ; Male ; Mice ; Mice, Inbred C57BL ; Proteome/metabolism*

In the past decade, relative proteomic quantification using isobaric labeling technology has developed into a key tool for comparing the expression of proteins in biological samples. Although its multiplexing capacity and flexibility make this a valuable technology for addressing various biological questions, its quantitative accuracy and precision still pose significant challenges to the reliability of its quantification results. Here, we give a detailed overview of the different kinds of isobaric mass tags and the advantages and disadvantages of the isobaric labeling method. We also discuss which precautions should be taken at each step of the isobaric labeling workflow, to obtain reliable quantification results in large-scale quantitative proteomics experiments. In the last section, we discuss the broad applications of the isobaric labeling technology in biological and clinical studies, with an emphasis on thermal proteome profiling and proteogenomics.
Proteome/metabolism* ; Proteomics/methods* ; Reproducibility of Results ; Tandem Mass Spectrometry/methods*

Ubiquitination, an essential post-transcriptional modification (PTM), plays a vital role in nearly every biological process, including development and growth. Despite its functions in plant reproductive development, its targets in rice panicles remain unclear. In this study, we used proteome-wide profiling of lysine ubiquitination in rice (O. sativa ssp. indica) young panicles. We created the largest ubiquitinome dataset in rice to date, identifying 1638 lysine ubiquitination sites on 916 unique proteins. We detected three conserved ubiquitination motifs, noting that acidic glutamic acid (E) and aspartic acid (D) were most frequently present around ubiquitinated lysine. Enrichment analysis of Gene Ontology (GO) annotations and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of these ubiquitinated proteins revealed that ubiquitination plays an important role in fundamental cellular processes in rice young panicles. Interestingly, enrichment analysis of protein domains indicated that ubiquitination was enriched on a variety of receptor-like kinases and cytoplasmic tyrosine and serine-threonine kinases. Furthermore, we analyzed the crosstalk between ubiquitination, acetylation, and succinylation, and constructed a potential protein interaction network within our rice ubiquitinome. Moreover, we identified ubiquitinated proteins related to pollen and grain development, indicating that ubiquitination may play a critical role in the physiological functions in young panicles. Taken together, we reported the most comprehensive lysine ubiquitinome in rice so far, and used it to reveal the functional role of lysine ubiquitination in rice young panicles.
Acetylation ; Lysine/metabolism* ; Oryza/metabolism* ; Plant Proteins/metabolism* ; Protein Interaction Maps ; Protein Processing, Post-Translational ; Proteome/metabolism* ; Ubiquitin/metabolism* ; Ubiquitination

BACKGROUND: Irritable bowel syndrome (IBS) is one of the most common functional intestinal diseases, but its pathogenesis is still unknown. The present study aimed to screen the differentially expressed proteins in the mucosa of colon between IBS with diarrhea (IBS-D) patients and the healthy controls. METHODS: Forty-two IBS-D patients meeting the Rome III diagnostic criteria and 40 control subjects from July 2007 to June 2009 in Chinese PLA General Hospital were enrolled in the present study. We examined the protein expression profiles in mucosa of colon corresponding to IBS-D patients (n = 5) and controls (n = 5) using 2-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS). Secondly, Western blot and immunohistochemical analysis were carried out to validate the screened proteins in 27 IBS-D patients and 27 controls. Thirdly, high-performance liquid chromatography (HPLC) was further carried out to determine ATP concentration in the mucosa of colon between 10 IBS-D patients and 8 controls. Comparisons between 2 groups were performed by Student's t-test or Mann-Whitney U-test. RESULTS: Twelve differentially expressed proteins were screened out. The α-enolase (ENOA) in the sigmoid colon (0.917 ± 0.007 vs. 1.310 ± 0.100, t = 2.643, P = 0.017) and caecum (0.765 ± 0.060 vs. 1.212 ± 0.122, t = 2.225, P = 0.023), Isobutyryl-CoA dehydrogenase (ACAD8) in the sigmoid colon (1.127 ± 0.201 vs. 1.497 ± 0.392, t = 7.093, P = 0.008) of the IBS-D group were significantly lower while acetyl-CoA acetyltransferase (CT) in the caecum (2.453 ± 0.422 vs. 0.931 ± 0.652, t = 8.363, P = 0.015) and ATP synthase subunit d (ATP5H) in the sigmoid (0.843 ± 0.042 vs. 0.631 ± 0.042, t = 8.613,P = 0.007) of the IBS-D group was significantly higher, compared with the controls. The ATP concentration in the mucosa of the sigmoid colon in IBS-D group was significantly lower than that of control group (0.470 [0.180, 1.360] vs. 5.350 [2.230, 7.900], U = 55, P < 0.001). CONCLUSIONS Many proteins related to energy metabolism presented differential expression patterns in the mucosa of colon of the IBS-D patients. The abnormalities in energy metabolism may be involved in the pathogenesis of IBS which deserves more studies to elucidate.
Adenosine Triphosphate ; metabolism ; Adult ; Blotting, Western ; Colon ; metabolism ; pathology ; Diarrhea ; enzymology ; metabolism ; pathology ; Electrophoresis, Gel, Two-Dimensional ; Energy Metabolism ; genetics ; physiology ; Female ; Humans ; Immunohistochemistry ; Intestinal Mucosa ; enzymology ; metabolism ; pathology ; Irritable Bowel Syndrome ; enzymology ; metabolism ; pathology ; Male ; Mass Spectrometry ; Middle Aged ; Proteome ; metabolism

PURPOSE: Chronic rhinosinusitis (CRS) is a complex immunological condition, and novel experimental modalities are required to explore various clinical and pathophysiological endotypes; mere evaluation of nasal polyp (NP) status is inadequate. Therefore, we collected patient nasal secretions on filter paper and characterized the proteomes. METHODS: We performed liquid chromatography-mass spectrometry (MS)/MS in the data-dependent acquisition (DDA) and data-independent acquisition (DIA) modes. Nasal secretions were collected from 10 controls, 10 CRS without NPs (CRSsNP) and 10 CRS with NPs (CRSwNP). We performed Orbitrap MS-based proteomic analysis in the DDA (5 controls, 5 CRSsNP and 5 CRSwNP) and the DIA (5 controls, 5 CRSsNP and 5 CRSwNP) modes, followed by a statistical analysis and a hierarchical clustering to identify differentially expressed proteins in the 3 groups. RESULTS: We identified 2,020 proteins in nasal secretions. Canonical pathway analysis and gene ontology (GO) evaluation revealed that interleukin (IL)-7, IL-9, IL-17A and IL-22 signaling and neutrophil-mediated immune responses like neutrophil degranulation and activation were significantly increased in CRSwNP compared to control. The GO terms related to the iron ion metabolism that may be associated with CRS and NP development. CONCLUSIONS: Collection of nasal secretions on the filter paper is a practical and non-invasive method for in-depth study of nasal proteomics. Our proteomic signatures also support that Asian NPs could be characterized as non-eosinophilic inflammation features. Therefore, the proteomic profiling of nasal secretions from CRS patients may enhance our understanding of CRS endotypes.
Asian Continental Ancestry Group ; Gene Ontology ; Humans ; Inflammation ; Interleukin-17 ; Interleukin-9 ; Interleukins ; Iron ; Metabolism ; Methods ; Nasal Polyps ; Neutrophils ; Proteome ; Proteomics ; Sinusitis ; Spectrum Analysis

The signaling network of the mitochondrial unfolded protein response (UPR(mt)) and mitohormesis is a retrograde signaling pathway through which mitochondria-to-nucleus communication occurs in organisms. Recently, it has been shown that the UPR(mt) is closely associated with metabolic disorders and conditions involving insulin resistance, such as alcoholic and non-alcoholic fatty liver and fibrotic liver disease. Scientific efforts to understand the UPR(mt) and mitohormesis, as well as to establish the mitochondrial proteome, have established the importance of mitochondrial quality control in the development and progression of metabolic liver diseases, including non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). In this review, we integrate and discuss the recent data from the literature on the UPR(mt) and mitohormesis in metabolic liver diseases, including NAFLD/NASH and fibrosis.
Alcoholics ; Fatty Liver ; Fibrosis ; Humans ; Insulin Resistance ; Liver Diseases ; Metabolism ; Mitochondria ; Non-alcoholic Fatty Liver Disease ; Obesity ; Proteome ; Quality Control ; Unfolded Protein Response