Obesity-related acetylcholinesterase elevation is reversed following laparoscopic sleeve gastrectomy

Shenhar‐Tsarfaty, Shani; Sherf-Dagan, Shiri; Berman, Galia; Webb, Muriel; Raziel, Asnat; Keidar, Andrei; Goitein, David; Sakran, Nasser; Zwang, Eti; Shapira, Itzhak; Zeltser, David; Berliner, Shlomo; Rogowski, Ori; Shibolet, Oren; Zelber‐Sagi, Shira

doi:10.1038/s41366-018-0014-4

Cited by 13 publications

(10 citation statements)

References 53 publications

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“…NR3C1, which is targeted by He Ye, is related to the etiology of obesity, the control of which will lead to an improvement in obesity-related disorders (Majer-Łobodzińska and Adamiec-Mroczek, 2017). Moreover, DDP4 (targeted by Zhi Qiao) and ACHE (targeted by Ling Zhi) play a significant role in obesity, and modulating their activity may be of great utility in obesity treatment (Valerio et al, 2017; Shenhar-Tsarfaty et al, 2019).…”

Section: Resultsmentioning

confidence: 99%

Systems Pharmacology-Based Method to Assess the Mechanism of Action of Weight-Loss Herbal Intervention Therapy for Obesity

et al. 2019

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Obesity is a multi-factorial chronic disease that has become a serious, prevalent, and refractory public health challenge globally because of high rates of various complications. Traditional Chinese medicines (TCMs) as a functional food are considered to be a valuable and readily available resource for treating obesity because of their better therapeutic effects and reduced side effects. However, their “multi-compound” and “multi-target” features make it extremely difficult to interpret the potential mechanism underlying the anti-obesity effects of TCMs from a holistic perspective. An innovative systems-pharmacology approach was employed, which combined absorption, distribution, metabolism, and excretion screening and multiple target fishing, gene ontology enrichment analysis, network pharmacology, and pathway analysis to explore the potential therapeutic mechanism of weight-loss herbal intervention therapy in obesity and related diseases. The current study provides a promising approach to facilitate the development and discovery of new botanical drugs.

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Section: Resultsmentioning

confidence: 99%

Systems Pharmacology-Based Method to Assess the Mechanism of Action of Weight-Loss Herbal Intervention Therapy for Obesity

et al. 2019

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“…The altered expression of genes including ERBB2 [ 38 ], DACT1 [ 39 ], ARAP1 [ 40 ], MYH9 [ 41 ], INPPL1 [ 42 ], SARM1 [ 43 ], NOTCH1 [ 44 ], ROBO1 [ 45 ], MAPK8IP1 [ 46 ], ANK1 [ 47 ], SARM1 [ 43 ], SREBF2 [ 48 ], SIK1 [ 49 ], PASK (PAS domain-containing serine/threonine kinase) [ 50 ], NOS2 [ 51 ], OAS3 [ 52 ], KL (klotho) [ 53 ], PECAM1 [ 54 ], S100A12 [ 55 ], S100P [ 56 ], BATF3 [ 57 ], PLEK (pleckstrin) [ 58 ], ALOX5 [ 59 ], ARG1 [ 60 ], CXCL8 [ 61 ], CXCR1 [ 62 ], PTAFR (platelet-activating factor receptor) [ 63 ], PYGL (glycogen phosphorylase L) [ 64 ], TCF4 [ 65 ], CAMP (cathelicidin antimicrobial peptide) [ 66 ], RUNX2 [ 67 ], PLA2G2A [ 68 ], GCG (glucagon) [ 69 ], RARRES2 [ 70 ] and HAP1 [ 71 ] in diabetes mellitus was reported to be an independent prognostic factors. ACHE (acetylcholinesterase) [ 72 ], FGFR3 [ 73 ], VLDLR (very-low-density lipoprotein receptor) [ 74 ], SHC1 [ 75 ], HDAC6 [ 76 ], CHRNA2 ...…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics and Next-Generation Data Analysis for Identification of Genes and Molecular Pathways Involved in Subjects with Diabetes and Obesity

Ganekal

Vastrad²,

Kavatagimath

et al. 2023

Medicina

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Background and Objectives: A subject with diabetes and obesity is a class of the metabolic disorder. The current investigation aimed to elucidate the potential biomarker and prognostic targets in subjects with diabetes and obesity. Materials and Methods: The next-generation sequencing (NGS) data of GSE132831 was downloaded from Gene Expression Omnibus (GEO) database. Functional enrichment analysis of DEGs was conducted with ToppGene. The protein–protein interactions network, module analysis, target gene–miRNA regulatory network and target gene–TF regulatory network were constructed and analyzed. Furthermore, hub genes were validated by receiver operating characteristic (ROC) analysis. A total of 872 DEGs, including 439 up-regulated genes and 433 down-regulated genes were observed. Results: Second, functional enrichment analysis showed that these DEGs are mainly involved in the axon guidance, neutrophil degranulation, plasma membrane bounded cell projection organization and cell activation. The top ten hub genes (MYH9, FLNA, DCTN1, CLTC, ERBB2, TCF4, VIM, LRRK2, IFI16 and CAV1) could be utilized as potential diagnostic indicators for subjects with diabetes and obesity.The hub genes were validated in subjects with diabetes and obesity. Conclusion: This investigation found effective and reliable molecular biomarkers for diagnosis and prognosis by integrated bioinformatics analysis, suggesting new and key therapeutic targets for subjects with diabetes and obesity.

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“…The mRNA expression of ACHE was significantly upregulated in response to acute AC2-26 treatment, in the current study. Previous studies have suggested impaired sympathetic/parasympathetic response and reduced cholinergic blockade may be responsible for the inflammation and adverse metabolic sequelae observed in obesity [ 80 ]. However, short-term cholinergic blockade with atropine; a competitive antagonist of the acetylcholine receptor enhanced insulin sensitivity in both human lean and abdominal obese subjects [ 81 ].…”

Section: Discussionmentioning

confidence: 99%

Suppression of Anti-Inflammatory Mediators in Metabolic Disease May Be Driven by Overwhelming Pro-Inflammatory Drivers

Sajid

Zariwala²,

Mackenzie³

et al. 2022

Nutrients

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Obesity is a multifactorial disease and is associated with an increased risk of developing metabolic syndrome and co-morbidities. Dysregulated expansion of the adipose tissue during obesity induces local tissue hypoxia, altered secretory profile of adipokines, cytokines and chemokines, altered profile of local tissue inflammatory cells leading to the development of low-grade chronic inflammation. Low grade chronic inflammation is considered to be the underlying mechanism that increases the risk of developing obesity associated comorbidities. The glucocorticoid induced protein annexin A1 and its N-terminal peptides are anti-inflammatory mediators involved in resolving inflammation. The aim of the current study was to investigate the role of annexin A1 in obesity and associated inflammation. To achieve this aim, the current study analysed data from two feasibility studies in clinical populations: (1) bariatric surgery patients (Pre- and 3 months post-surgery) and (2) Lipodystrophy patients. Plasma annexin A1 levels were increased at 3-months post-surgery compared to pre-surgery (1.2 ± 0.1 ng/mL, n = 19 vs. 1.6 ± 0.1 ng/mL, n = 9, p = 0.009) and positively correlated with adiponectin (p = 0.009, r = 0.468, n = 25). Plasma annexin A1 levels were decreased in patients with lipodystrophy compared to BMI matched controls (0.2 ± 0.1 ng/mL, n = 9 vs. 0.97 ± 0.1 ng/mL, n = 30, p = 0.008), whereas CRP levels were significantly elevated (3.3 ± 1.0 µg/mL, n = 9 vs. 1.4 ± 0.3 µg/mL, n = 31, p = 0.0074). The roles of annexin A1 were explored using an in vitro cell based model (SGBS cells) mimicking the inflammatory status that is observed in obesity. Acute treatment with the annexin A1 N-terminal peptide, AC2-26 differentially regulated gene expression (including PPARA (2.8 ± 0.7-fold, p = 0.0303, n = 3), ADIPOQ (2.0 ± 0.3-fold, p = 0.0073, n = 3), LEP (0.6 ± 0.2-fold, p = 0.0400, n = 3), NAMPT (0.4 ± 0.1-fold, p = 0.0039, n = 3) and RETN (0.1 ± 0.03-fold, p < 0.0001, n = 3) in mature obesogenic adipocytes indicating that annexin A1 may play a protective role in obesity and inflammation. However, this effect may be overshadowed by the continued increase in systemic inflammation associated with rapid tissue expansion in obesity.

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Obesity-related acetylcholinesterase elevation is reversed following laparoscopic sleeve gastrectomy

Abstract: Obesity-related AChE resistance phenotype may be reversed following LSG and correlates with metabolic outcomes. Further long-term studies will be needed to validate and evaluate the beneficial effect of AChE reduction post bariatric surgery.

Cited by 13 publications

References 53 publications

Systems Pharmacology-Based Method to Assess the Mechanism of Action of Weight-Loss Herbal Intervention Therapy for Obesity

Systems Pharmacology-Based Method to Assess the Mechanism of Action of Weight-Loss Herbal Intervention Therapy for Obesity

Bioinformatics and Next-Generation Data Analysis for Identification of Genes and Molecular Pathways Involved in Subjects with Diabetes and Obesity

Suppression of Anti-Inflammatory Mediators in Metabolic Disease May Be Driven by Overwhelming Pro-Inflammatory Drivers

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