Changes in the Proteome Profile of People Achieving Remission of Type 2 Diabetes after Bariatric Surgery

Iqbal, Zohaib; Fachim, Helene; Gibson, John M.; Baričević-Jones, Ivona; Campbell, Amy E.; Geary, Bethany; Donn, Rachelle; Hamarashid, Dashne; Syed, Akheel A.; Whetton, Anthony D.; Soran, Handrean; Heald, Adrian

doi:10.3390/jcm10163659

Cited by 6 publications

(8 citation statements)

References 94 publications

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“…SWATH-MS proteomics was carried out on 29 plasma samples with the following sample subgroups: baseline samples, pre-bariatric surgery samples (taken at 4 months prior to MBS (n = 10); post-bariatric surgery samples, 6 months follow up (n = 10); and post-bariatric surgery samples, 12 months follow up (n = 9). Details of the SWATH-MS analysis are described in our previous publication [17]. Percentage changes were calculated for each of these parameters at 6 and 12 months compared to baseline.…”

Section: Methodsmentioning

confidence: 99%

“…bioconductor.org). We identified 38 proteins with significant fold changes between baseline and 6 months, and 25 proteins with significant fold changes between baseline and 12 months [17]. The detailed methods for SWATH-MS analysis were described previ-ously [17].…”

Section: Identification Of Proteinsmentioning

confidence: 99%

“…We identified 38 proteins with significant fold changes between baseline and 6 months, and 25 proteins with significant fold changes between baseline and 12 months [17]. The detailed methods for SWATH-MS analysis were described previ-ously [17]. In summary, plasma samples (10 µL) were immunodepleted and concentrated afterwards using protein-depletion spin columns and Amicon filters, respectively.…”

Section: Identification Of Proteinsmentioning

confidence: 99%

“…When major metabolic change occurs, blood protein components have a key role and can be altered significantly. We have recently shown significant changes in the proteome for eight proteins at 6 and 12 months post-BS, and several of these are key components in metabolic and inflammatory pathways [17]. We now set out to identify potential proteins related to inflammatory markers (IL6, TNFα and C-reactive protein-CRP) in plasma samples of people achieving remission of T2DM following MBS.…”

Section: Introductionmentioning

confidence: 99%

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Relationship between the Plasma Proteome and Changes in Inflammatory Markers after Bariatric Surgery

Fachim

Iqbal

Gibson

et al. 2021

Cells

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Severe obesity is a disease associated with multiple adverse effects on health. Metabolic bariatric surgery (MBS) can have significant effects on multiple body systems and was shown to improve inflammatory markers in previous short-term follow-up studies. We evaluated associations between changes in inflammatory markers (CRP, IL6 and TNFα) and circulating proteins after MBS. Methods: Sequential window acquisition of all theoretical mass spectra (SWATH-MS) proteomics was performed on plasma samples taken at baseline (pre-surgery) and 6 and 12 months after MBS, and concurrent analyses of inflammatory/metabolic parameters were carried out. The change in absolute abundances of those proteins, showing significant change at both 6 and 12 months, was tested for correlation with the absolute and percentage (%) change in inflammatory markers. Results: We found the following results: at 6 months, there was a correlation between %change in IL-6 and fold change in HSPA4 (rho = −0.659; p = 0.038) and in SERPINF1 (rho = 0.714, p = 0.020); at 12 months, there was a positive correlation between %change in IL-6 and fold change in the following proteins—LGALS3BP (rho = 0.700, p = 0.036), HSP90B1 (rho = 0.667; p = 0.05) and ACE (rho = 0.667, p = 0.05). We found significant inverse correlations at 12 months between %change in TNFα and the following proteins: EPHX2 and ACE (for both rho = −0.783, p = 0.013). We also found significant inverse correlations between %change in CRP at 12 months and SHBG (rho = −0.759, p = 0.029), L1CAM (rho = −0.904, p = 0.002) and AMBP (rho = −0.684, p = 0.042). Conclusion: Using SWATH-MS, we identified several proteins that are involved in the inflammatory response whose levels change in patients who achieve remission of T2DM after bariatric surgery in tandem with changes in IL6, TNFα and/or CRP. Future studies are needed to clarify the underlying mechanisms in how MBS decreases low-grade inflammation.

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Section: Methodsmentioning

confidence: 99%

Section: Identification Of Proteinsmentioning

confidence: 99%

Section: Identification Of Proteinsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Relationship between the Plasma Proteome and Changes in Inflammatory Markers after Bariatric Surgery

Fachim

Iqbal

Gibson

et al. 2021

Cells

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“…LRG1 could be further excavated as a potential target for the pathological progress of diabetic kidney disease, including glomerular lesions in diabetes (Fu et al, 2018;Iqbal et al, 2021), lysosomal function related Type 1 diabetes (Singh et al, 2017), and nephropathy in type 2 diabetes. (Liu et al, 2017;Gurung et al, 2021).…”

Section: Part Three: Lrg1 Involved In Endocrine Diseasesmentioning

confidence: 99%

Research Progress on Leucine-Rich Alpha-2 Glycoprotein 1: A Review

Zou

Chen

et al. 2022

Front. Pharmacol.

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Leucine-rich alpha⁃2 glycoprotein 1 (LRG1) is an important member of the leucine-rich repetitive sequence protein family. LRG1 was mainly involved in normal physiological activities of the nervous system, such as synapse formation, synapse growth, the development of nerve processes, neurotransmitter transfer and release, and cell adhesion molecules or ligand-binding proteins. Also, LRG1 affected the development of respiratory diseases, hematological diseases, endocrine diseases, tumor diseases, eye diseases, cardiovascular diseases, rheumatic immune diseases, infectious diseases, etc. LRG1 was a newly discovered important upstream signaling molecule of transforming growth factor⁃β (TGF⁃β) that affected various pathological processes through the TGF⁃β signaling pathway. However, research on LRG1 and its involvement in the occurrence and development of diseases was still in its infancy and the current studies were mainly focused on proteomic detection and basic animal experimental reports. We could reasonably predict that LRG1 might act as a new direction and strategy for the treatment of many diseases.

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Plasma proteome profiling reveals the therapeutic effects of the PPAR pan-agonist chiglitazar on insulin sensitivity, lipid metabolism, and inflammation in type 2 diabetes

Wang,

Hou

et al. 2024

Sci Rep

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Chiglitazar is a novel peroxisome proliferator-activated receptor (PPAR) pan-agonist, which passed phase III clinical trials and was newly approved in China for use as an adjunct to diet and exercise in glycemic control in adult patients with Type 2 Diabetes (T2D). To explore the circulating protein signatures associated with the administration of chiglitazar in T2D patients, we conducted a comparative longitudinal study using plasma proteome profiling. Of the 157 T2D patients included in the study, we administered chiglitazar to a specific group, while the controls were given either placebo or sitagliptin. The plasma proteomes were profiled at baseline and 12 and 24 weeks post-treatment using data-independent acquisition mass spectrometry (DIA-MS). Our study indicated that 13 proteins were associated with chiglitazar treatment in T2D patients, including 10 up-regulated proteins (SHBG, TF, APOA2, APOD, GSN, MBL2, CFD, PGLYRP2, A2M, and APOA1) and 3 down-regulated proteins (PRG4, FETUB, and C2) after treatment, which were implicated in the regulation of insulin sensitivity, lipid metabolism, and inflammation response. Our study provides insight into the response of chiglitazar treatment from a proteome perspective and demonstrates the multi-faceted effects of chiglitazar in T2D patients, which will help the clinical application of chiglitazar and further study of its action mechanism.

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Changes in the Proteome Profile of People Achieving Remission of Type 2 Diabetes after Bariatric Surgery

Cited by 6 publications

References 94 publications

Relationship between the Plasma Proteome and Changes in Inflammatory Markers after Bariatric Surgery

Relationship between the Plasma Proteome and Changes in Inflammatory Markers after Bariatric Surgery

Research Progress on Leucine-Rich Alpha-2 Glycoprotein 1: A Review

Plasma proteome profiling reveals the therapeutic effects of the PPAR pan-agonist chiglitazar on insulin sensitivity, lipid metabolism, and inflammation in type 2 diabetes

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