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Reduction in endotoxemia, oxidative and inflammatory stress, and insulin resistance after Roux-en-Y gastric bypass surgery in patients with morbid obesity and type 2 diabetes mellitus
Abstract
Background Roux-en-Y gastric bypass (RYGB) results in profound weight loss and resolution of type 2 diabetes mellitus (T2DM). The mechanism of this remarkable transition remains poorly defined. It has been proposed that endotoxin (lipopolysaccharide [LPS]) sets inflammatory tone, triggers weight gain, and initiates T2DM. Because RYGB may diminish LPS from endogenous and exogenous sources, we hypothesized that LPS and the associated cascade of oxidative and inflammatory stress would diminish after RYGB.Methods Fifteen adults with morbid obesity and T2DM undergoing RYGB were studied. After an overnight fast, a baseline blood sample was collected the morning of surgery and at 180 days to assess changes in glycemia, insulin resistance, LPS, mononuclear cell nuclear factor (NF)-κB binding and mRNA expression of CD14, TLR-2, TLR-4, and markers of inflammatory stress.Results At 180 days after RYGB, subjects had a significant decrease in body mass index (52.1 ± 13.0 to 40.4 ± 11.1), plasma glucose (148 ± 8 to 101 ± 4 mg/dL), insulin (18.5 ± 2.2 mμU/mL to 8.6 ± 1.0 mμU/mL) and HOMA-IR (7.1 ± 1.1 to 2.1 ± 0.3). Plasma LPS significantly reduced by 20 ± 5% (0.567 ± 0.033 U/mL to 0.443 ± 0.022 E U/mL). NF-κB DNA binding decreased significantly by 21 ± 8%, whereas TLR-4, TLR-2, and CD-14 expression decreased significantly by 25 ± 9%, 42 ± 8%, and 27 ± 10%, respectively. Inflammatory mediators CRP, MMP-9, and MCP-1 decreased significantly by 47 ± 7% (10.7 ± 1.6 mg/L to 5.8 ± 1.0 mg/L), 15 ± 6% (492 ± 42 ng/mL to 356 ± 26 ng/mL) and 11 ± 4% (522 ± 35 ng/mL to 466 ± 35 ng/mL), respectively.Conclusion LPS, NF-κB DNA binding, TLR-4, TLR-2, and CD14 expression, CRP, MMP-9, and MCP-1 decreased significantly after RYGB. The mechanism underlying resolution of insulin resistance and T2DM after RYGB may be attributable, at least in part, to the reduction of endotoxemia and associated proinflammatory mediators.
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“In addition, intranuclear binding of nuclear factor kappa B, a major proinflammatory transcription factor, also fell.”
From Bariatric surgery: remission of inflammation, cardiometabolic benefits, and common adverse effects (2020) · cites this paper as [15]
In the citing paper
“This observation was also noted in 2012, 6 months after a Roux-en-Y gastric bypass (RYGB) procedure [15], where a reduction in plasma concentrations of endotoxin was observed.”
From Bariatric surgery: remission of inflammation, cardiometabolic benefits, and common adverse effects (2020) · cites this paper as [15]
In the citing paper
“Substantial decreases in the expression of toll-like receptors, TLR-4 and TLR-2 (the respective receptors for endotoxin and Gram-positive bacterial products), occurred in mononuclear cells.”
From Bariatric surgery: remission of inflammation, cardiometabolic benefits, and common adverse effects (2020) · cites this paper as [15]
In the citing paper
“Concomitant reductions in plasma concentrations of matrix metallopeptidase (MMP)-9 and C-reactive protein (CRP) were seen and there was also a reduction in the expression of CD14, the marker of activated monocytes.”
From Bariatric surgery: remission of inflammation, cardiometabolic benefits, and common adverse effects (2020) · cites this paper as [15]
In the citing paper
“In addition, there was a parallel reduction in fasting glucose and insulin concentrations, reflected in reduced Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), an index of insulin resistance.”
From Bariatric surgery: remission of inflammation, cardiometabolic benefits, and common adverse effects (2020) · cites this paper as [15]
In the citing paper
“Beyond gastrointestinal derived signals and feeding behavior alteration, contributing factors include the reductions in endotoxemia/inflammation and insulin resistance after bariatric surgery [15].”
From Bariatric surgery: remission of inflammation, cardiometabolic benefits, and common adverse effects (2020) · cites this paper as [15]
Citations
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Bariatric Surgery: A Systematic Review and Meta-analysis
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Self-citationToll-like Receptor-4 Mediates Lipopolysaccharide-induced Signal Transduction
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Human gut microbiota in obesity and after gastric bypass
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Cited by
Sorted by citations
Chait, A., & den Hartigh, L. J. (2020) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2020.00022 · Cited by 1,529
“Such metabolic endotoxemia is reduced following antibiotic treatment (681) or RYGB surgery-induced weight loss (627).”
BackgroundHuman gut microbiome: Hopes, threats and promises
Cani, P. D. (2018) · Gut · doi:10.1136/gutjnl-2018-316723 · Cited by 1,386
Systemic Effects of Inflammation on Health during Chronic HIV Infection
Deeks, S. G., Tracy, R. P., & Douek, D. C. (2013) · Immunity · doi:10.1016/j.immuni.2013.10.001 · Cited by 910
“…pancreatitis, graft-versus-host disease, excessive alcohol consumption, and obesity and diabetes, and might even contribute to aging (Lassenius et al., 2011; Monte et al., 2012; Nalle and Turner, 2012; Pussinen et al., 2007, 2011; Sandler et al., 2011a; Tran and Greenwood-Van Meerveld, 2013).”
How Probiotics Affect the Microbiota
Wieërs, G., Belkhir, L., Enaud, R., Leclercq, S., de Foy, J.-M. P., Dequenne, I., de Timary, P., & Cani, P. D. (2020) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2019.00454 · Cited by 557
“Importantly, this finding was later confirmed in several large human cohorts (Amar et al., 2008; Gummesson et al., 2011; Lassenius et al., 2011; Laugerette et al., 2011; Monte et al., 2011; Pussinen et al., 2011; Horton et al., 2014; Jayashree et al., 2014; Radilla-Vazquez et al., 2016; Gomes et al., 2017).”
ResultMetabolic endotoxemia with obesity: Is it real and is it relevant?
Boutagy, N. E., McMillan, R. P., Frisard, M. I., & Hulver, M. W. (2016) · Biochimie · doi:10.1016/j.biochi.2015.06.020 · Cited by 413
Metadata
- Authors
- Monte, S. V., Caruana, J. A., Ghanim, H., Sia, C. L., Korzeniewski, K., Schentag, J. J., & Dandona, P.
- Affiliations
- University at Buffalo, State University of New York (US)
- Sisters of Charity Hospital (US)
- Kaleida Health (US)
- Corresponding author
- Monte, Scott V.
- Venue
- Surgery
- Publisher
- Elsevier BV
- Published
- 2012-04
- Volume
- 151
- Issue
- 4
- Pages
- 587-593
- ISSN
- 0039-6060 (ISSN-L)
- OpenAlex
- W1985684171
- Cited by
- 143
- References
- 31
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 6 · 2023: 7 · 2022: 11 · 2021: 18 · 2020: 14 · 2019: 13 · 2018: 7 · 2017: 9 · 2016: 8 · 2015: 14 · 2014: 10 · 2013: 15 · 2012: 6
- FWCI
- 10.14
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Surgery (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01dk069805-04)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01-DK069805, R01DK075877)
- Topics
- Health Sciences › Medicine › Surgery › Bariatric Surgery and Outcomes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Surgery › Minimally Invasive Surgical Techniques
- Keywords
- Roux-en-Y gastric bypass, morbid obesity, type 2 diabetes, endotoxemia, lipopolysaccharide, insulin resistance, oxidative stress, inflammatory stress, NF-κB, Toll-like receptors, CD14, TLR4, TLR2, weight loss, bariatric surgery, C-reactive protein, MMP-9
- MeSH terms
- Adult, Anthropometry, Diabetes Mellitus, Type 2, Female, Humans, Inflammation, Insulin Resistance, Leukocytes, Mononuclear, Lipopolysaccharides, Male, Middle Aged, Obesity, Morbid, Gastric Bypass, NF-kappa B, Treatment Outcome, Oxidative Stress, Lipopolysaccharide Receptors, Endotoxemia, Toll-Like Receptor 4
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