Dataset Information

IGFBP-2 partly mediates the early metabolic improvements caused by bariatric surgery.

ABSTRACT: Insulin-like growth factor-binding protein (IGFBP)-2 is a circulating biomarker of cardiometabolic health. Here, we report that circulating IGFBP-2 concentrations robustly increase after different bariatric procedures in humans, reaching higher levels after biliopancreatic diversion with duodenal switch (BPD-DS) than after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). This increase is closely associated with insulin sensitization. In mice and rats, BPD-DS and RYGB operations also increase circulating IGFBP-2 levels, which are not affected by SG or caloric restriction. In mice, Igfbp2 deficiency significantly impairs surgery-induced loss in adiposity and early improvement in insulin sensitivity but does not affect long-term enhancement in glucose homeostasis. This study demonstrates that the modulation of circulating IGFBP-2 may play a role in the early improvement of insulin sensitivity and loss of adiposity brought about by bariatric surgery.

SUBMITTER: Faramia J

PROVIDER: S-EPMC8080239 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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IGFBP-2 partly mediates the early metabolic improvements caused by bariatric surgery.

Faramia Justine J Hao Zheng Z Mumphrey Michael B MB Townsend R Leigh RL Miard Stéphanie S Carreau Anne-Marie AM Nadeau Mélanie M Frisch Frédérique F Baraboi Elena-Dana ED Grenier-Larouche Thomas T Noll Christophe C Li Meng M Biertho Laurent L Marceau Simon S Hould Frédéric-Simon FS Lebel Stéfane S Morrison Christopher D CD Münzberg Heike H Richard Denis D Carpentier André C AC Tchernof André A Berthoud Hans-Rudolf HR Picard Frédéric F

Cell reports. Medicine 20210420 4

Insulin-like growth factor-binding protein (IGFBP)-2 is a circulating biomarker of cardiometabolic health. Here, we report that circulating IGFBP-2 concentrations robustly increase after different bariatric procedures in humans, reaching higher levels after biliopancreatic diversion with duodenal switch (BPD-DS) than after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). This increase is closely associated with insulin sensitization. In mice and rats, BPD-DS and RYGB operations also ...[more]

PMID: 33948578

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Project description:Obesity and its metabolic complications are associated with lower grey matter and white matter densities, whereas weight loss after bariatric surgery leads to an increase in both measures. These increases in grey and white matter density are significantly associated with post-operative weight loss and improvement of the metabolic/inflammatory profiles. While our recent studies demonstrated widespread increases in white matter density 4 and 12 months after bariatric surgery, it is not clear if these changes persist over time. The underlying mechanisms also remain unknown. In this regard, numerous studies demonstrate that the enlargement or hypertrophy of mature adipocytes, particularly in the visceral fat compartment, is an important marker of adipose tissue dysfunction and obesity-related cardiometabolic abnormalities. We aimed (i) to assess whether the increases in grey and white matter densities previously observed at 12 months are maintained 24 months after bariatric surgery; (ii) to examine the association between these structural brain changes and adiposity and metabolic markers 24 months after bariatric surgery; and (iii) to examine the association between abdominal adipocyte diameter at the time of surgery and post-surgery grey and white matter densities changes. Thirty-three participants undergoing bariatric surgery were recruited. Grey and white matter densities were assessed from T1-weighted magnetic resonance imaging scans acquired prior to and 4, 12 and 24 months post-surgery using voxel-based morphometry. Omental and subcutaneous adipose tissue samples were collected during the surgical procedure. Omental and subcutaneous adipocyte diameters were measured by microscopy of fixed adipose tissue samples. Linear mixed-effects models were performed controlling for age, sex, surgery type, initial body mass index, and initial diabetic status. The average weight loss at 24 months was 33.6 ± 7.6%. A widespread increase in white matter density was observed 24 months post-surgery mainly in the cerebellum, brainstem and corpus callosum (P < 0.05, false discovery rate) as well as some regions in grey matter density. Greater omental adipocyte diameter at the time of surgery was associated with greater changes in total white matter density at 24 months (P = 0.008). A positive trend was observed between subcutaneous adipocyte diameter at the time of surgery and changes in total white matter density at 24 months (P = 0.05). Our results show prolonged increases in grey and white matter densities up to 24 months post-bariatric surgery. Greater preoperative omental adipocyte diameter is associated with greater increases in white matter density at 24 months, suggesting that individuals with excess visceral adiposity might benefit the most from surgery.

Project description:ContextAltered cytokine levels and chronic low-grade inflammation contribute to metabolic dysfunction in obesity. The extent of cytokine changes and their impact on metabolic improvements after bariatric surgery have not been fully explored.ObjectiveTo compare 76 circulating cytokines, chemokines, and secreted cytokine receptors in subjects with obesity and lean subjects and determine how these cytokines are altered by bariatric surgery.Design, setting, and participantsA total of 37 patients with obesity and 37 lean patients in a cross-sectional study at an academic medical center. We also investigated cytokine changes in 25 patients with obesity after bariatric surgery.InterventionBariatric surgery (Roux-en-Y gastric bypass and vertical sleeve gastrectomy).Main outcome measuresQuantification of 76 circulating cytokines, chemokines, and secreted cytokine receptors.ResultsA total of 13 cytokines were significantly higher, and 4 lower, in patients with obesity relative to lean controls. Soluble vascular endothelial growth factor receptor 2 (sVEGFR2), soluble TNF receptor (sTNFR) 1, and sTNFR2 were positively correlated, and soluble receptor for advanced glycation end-products was inversely correlated, with weight and body mass index. sTNFR2 was positively correlated with fasting glucose, homeostatic model assessment of insulin resistance, and hemoglobin A1c. After bariatric surgery, adiponectin increased, and leptin decreased. Elevated sVEGFR2 levels in patients with obesity were decreased (P = 0.01), whereas reduced chemokine (C-X-C motif) ligand (CXCL) 12 levels in patients with obesity increased (P = 0.03) after surgery. Patients with higher soluble interleukin receptor (sIL) 1R2 and sIL-6R levels before surgery had greater weight loss after surgery (P < 0.05).ConclusionsWe demonstrate that chemokine (C-C motif) ligand (CCL) 14, sVEGFR2, and platelet-derived growth factor BB are elevated in obesity, and CXCL12, CCL11, and CCL27 are lower in obesity. We found clinically concordant directionality between lean and patients with obesity and before vs after surgery for six cytokines, suggesting that bariatric surgery shifted the cytokine profiles of patients with obesity toward that of lean controls.

Dataset Information

IGFBP-2 partly mediates the early metabolic improvements caused by bariatric surgery.

Publications

IGFBP-2 partly mediates the early metabolic improvements caused by bariatric surgery.

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