Intestinal Glucose Absorption Was Reduced by Vertical Sleeve Gastrectomy via Decreased Gastric Leptin Secretion

Hao, Dingjun; Hu, Chaojie; Bai, Jie; Peng, Miaomiao; Wang, Qingbo; Zhao, Ning; Wang, Yu; Wang, Guobin; Tao, Kaixiong; Wang, Geng; Xia, Zefeng

doi:10.1007/s11695-018-3351-4

Cited by 12 publications

(16 citation statements)

References 48 publications

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“…We also observed changes in the VAT metabolic gene profile with an upregulation of EHHADH -a peroxisomal enzyme responsible for beta oxidation of fatty acids -and related processes of fatty acid betaoxidation, peroxisome function, and amino acid metabolism. In keeping with the published human data showing decreased systemic and organ-specific leptin levels following sleeve gastrectomy, there was a reduction in the leptin (LEP) expression within the VAT of SG animals [29][30][31]. There was also a reduction in oxytocin receptor signaling, which partially controls adipogenesis and fat accumulation in fat-tissue depots [32].…”

Section: Rna Sequencing Reveals Gene Level Changes In Visceral Fat Imsupporting

confidence: 81%

“…Despite this, SG animals had improvements in glucose homeostasis, insulin resistance, and increased circulating GLP-1; all of which are hallmarks of post-SG physiology. [30] Specifically, when challenged with oral glucose, SG animals showed a dramatic reduction in systemic glucose levels 15 to 30 minutes post gavage with a corollary increase in serum GLP-1 expression at 15 minutes. This "glucose sink" phenomenon suggested increased tissue glucose uptake and utilization.…”

Section: Discussionmentioning

confidence: 99%

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Sleeve Gastrectomy enhances glucose utilization and remodels adipose tissue independent of weight loss

Harris

Mina

Čabarkapa

et al. 2019

Preprint

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Objective: Sleeve gastrectomy (SG) induces weight-loss independent improvements in glucose homeostasis by unknown mechanisms. We sought to identify the metabolic adaptations responsible for these improvements.Methods: Non-obese C57Bl6/J mice on standard chow underwent SG or sham surgery. Functional testing and indirect calorimetry were used to capture metabolic phenotypes. Tissuespecific glucose uptake was assessed by 18-FDG PET/CT and RNA sequencing was used for gene expression analysis.Results: In this model, SG induced durable improvements in glucose tolerance despite not causing lasting changes in weight, fat/lean mass, or food intake. Indirect calorimetry revealed post-SG animals had respiratory exchange ratios (RER) nearing 1.0 on average and had daily RER excursions above 1.0, indicating preferential glucose utilization and increased energy demand, respectively. Sham operated mice demonstrate normal RER feeding/fasting excursions. PET/CT showed increased avidity within white adipose depots. Finally, SG led to an upregulation in the transcriptional pathways involved in energy metabolism, adipocyte maturation, and adaptive and innate immune cell chemotaxis and differentiation within the visceral adipose tissue.Conclusions: SG induces a rapid, weight-loss independent shift towards glucose utilization and transcriptional remodeling of metabolic and immune pathways in visceral adipose tissue.

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Section: Rna Sequencing Reveals Gene Level Changes In Visceral Fat Imsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Sleeve Gastrectomy enhances glucose utilization and remodels adipose tissue independent of weight loss

Harris

Mina

Čabarkapa

et al. 2019

Preprint

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“…With regards to VSG, a lower glucose absorption in the small intestine has been shown (59, 62). Following VSG, a large part of the stomach is removed and therefore, there is a reduction in the leptin- and ghrelin-expressing cells.…”

Section: Glucose Absorptionmentioning

confidence: 99%

“…Therefore, after VSG surgery a negative correlation has been shown between ghrelin concentrations and insulin sensitivity and secretion (64). Gastric leptin is produced in the stomach and secreted into the small intestine, where it is believed to promote glucose absorption by enhancing the glucose transporter-2 (GLUT2) in the jejunum (62, 65). A recent study showed that after VSG surgery there was a decrease in glucose absorption which was enhanced with the addition of an oral gavage of leptin (62).…”

Section: Glucose Absorptionmentioning

confidence: 99%

Mechanisms Underlying Type 2 Diabetes Remission After Metabolic Surgery

et al. 2019

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Type 2 diabetes prevalence is increasing dramatically worldwide. Metabolic surgery is the most effective treatment for selected patients with diabetes and/or obesity. When compared to intensive medical therapy and lifestyle intervention, metabolic surgery has shown superiority in achieving glycemic improvement, reducing number of medications and cardiovascular risk factors, which translates in long-term benefits on cardiovascular morbidity and mortality. The mechanisms underlying diabetes improvement after metabolic surgery have not yet been clearly understood but englobe a complex interaction among improvements in beta cell function and insulin secretion, insulin sensitivity, intestinal gluconeogenesis, changes in glucose utilization, and absorption by the gut and changes in the secretory pattern and morphology of adipose tissue. These are achieved through different mediators which include an enhancement in gut hormones release, especially, glucagon-like peptide 1, changes in bile acids circulation, gut microbiome, and glucose transporters expression. Therefore, this review aims to provide a comprehensive appraisal of what is known so far to better understand the mechanisms through which metabolic surgery improves glycemic control facilitating future research in the field.

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“…The process of immunohistochemical staining was operated as previous report [ 33 ]. Briefly, the paraffin sections were heated at 60 ° C for 60 minutes, then dewaxed to xylene twice for 15 minutes and washed by gradient alcohol and distilled water for 5 minutes.…”

Section: Methodsmentioning

confidence: 99%

ARHGEF11 promotes proliferation and epithelial-mesenchymal transition of hepatocellular carcinoma through activation of β-catenin pathway

Hao¹,

Zhu²,

Lin³

et al. 2020

aging

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Rho guanine nucleotide exchange factor 11 (ARHGEF11) has been proved to promote tumor metastasis in glioblastoma and ovarian carcinoma. However, the role of ARHGEF11 in hepatocellular carcinoma (HCC) progression is largely unknown. Here, we found that ARHGEF11 was upregulated in HCC samples and highly metastatic hepatoma cell lines. Knockdown of ARHGEFF11 inhibited the cell proliferation and invasion in both HCCLM3 and SKHEP1 cell lines. Subsequent mechanistic investigation showed that downregulation of ARHGEF11 significantly attenuated β-catenin nuclear translocation, thereafter repressed the expression of ZEB1 and cyclinD1, finally contributing to inhibition of epithelial-mesenchymal transition (EMT) and cell cycle arrest. Moreover, high levels of ARHGEF11 were found to be associated with shorter disease free and overall survival. A prognostic nomogram model that integrated ARHGEF11, tumor size and BCLC classification showed good performance in predicting clinical outcomes of HCC patients. Overall, this study demonstrated that ARHGEF11 could promote proliferation and metastasis of HCC via activating β-catenin pathway, suggesting that ARHGEF11 might serve as a potential prognostic biomarker for HCC.

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Intestinal Glucose Absorption Was Reduced by Vertical Sleeve Gastrectomy via Decreased Gastric Leptin Secretion

Abstract: Our data demonstrated that the decreased secretion of gastric leptin in VSG results in a decrease in intestinal glucose absorption via modulation of GLUT2 translocation.

Cited by 12 publications

References 48 publications

Sleeve Gastrectomy enhances glucose utilization and remodels adipose tissue independent of weight loss

Sleeve Gastrectomy enhances glucose utilization and remodels adipose tissue independent of weight loss

Mechanisms Underlying Type 2 Diabetes Remission After Metabolic Surgery

ARHGEF11 promotes proliferation and epithelial-mesenchymal transition of hepatocellular carcinoma through activation of β-catenin pathway

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Intestinal Glucose Absorption Was Reduced by Vertical Sleeve Gastrectomy via Decreased Gastric Leptin Secretion

Abstract: Our data demonstrated that the decreased secretion of gastric leptin in VSG results in a decrease in intestinal glucose absorption via modulation of GLUT2 translocation.

Cited by 12 publications

References 48 publications

Sleeve Gastrectomy enhances glucose utilization and remodels adipose tissue independent of weight loss

Sleeve Gastrectomy enhances glucose utilization and remodels adipose tissue independent of weight loss

Mechanisms Underlying Type 2 Diabetes Remission After Metabolic Surgery

ARHGEF11 promotes proliferation and epithelial-mesenchymal transition of hepatocellular carcinoma through activation of &#x3B2;-catenin pathway

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ARHGEF11 promotes proliferation and epithelial-mesenchymal transition of hepatocellular carcinoma through activation of β-catenin pathway