Dataset Information

G-CSF partially mediates effects of sleeve gastrectomy on the bone marrow niche.

ABSTRACT: Bariatric surgeries are integral to the management of obesity and its metabolic complications. However, these surgeries cause bone loss and increase fracture risk through poorly understood mechanisms. In a mouse model, vertical sleeve gastrectomy (VSG) caused trabecular and cortical bone loss that was independent of sex, body weight, and diet, and this loss was characterized by impaired osteoid mineralization and bone formation. VSG had a profound effect on the bone marrow niche, with rapid loss of marrow adipose tissue, and expansion of myeloid cellularity, leading to increased circulating neutrophils. Following VSG, circulating granulocyte-colony stimulating factor (G-CSF) was increased in mice, and was transiently elevated in a longitudinal study of humans. Elevation of G-CSF was found to recapitulate many effects of VSG on bone and the marrow niche. In addition to stimulatory effects of G-CSF on myelopoiesis, endogenous G-CSF suppressed development of marrow adipocytes and hindered accrual of peak cortical and trabecular bone. Effects of VSG on induction of neutrophils and depletion of marrow adiposity were reduced in mice deficient for G-CSF; however, bone mass was not influenced. Although not a primary mechanism for bone loss with VSG, G-CSF plays an intermediary role for effects of VSG on the bone marrow niche.

SUBMITTER: Li Z

PROVIDER: S-EPMC6546463 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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G-CSF partially mediates effects of sleeve gastrectomy on the bone marrow niche.

Li Ziru Z Hardij Julie J Evers Simon S SS Hutch Chelsea R CR Choi Sarah M SM Shao Yikai Y Learman Brian S BS Lewis Kenneth T KT Schill Rebecca L RL Mori Hiroyuki H Bagchi Devika P DP Romanelli Steven M SM Kim Ki-Suk KS Bowers Emily E Griffin Cameron C Seeley Randy J RJ Singer Kanakadurga K Sandoval Darleen A DA Rosen Clifford J CJ MacDougald Ormond A OA

The Journal of clinical investigation 20190506 6

Bariatric surgeries are integral to the management of obesity and its metabolic complications. However, these surgeries cause bone loss and increase fracture risk through poorly understood mechanisms. In a mouse model, vertical sleeve gastrectomy (VSG) caused trabecular and cortical bone loss that was independent of sex, body weight, and diet, and this loss was characterized by impaired osteoid mineralization and bone formation. VSG had a profound effect on the bone marrow niche, with rapid loss ...[more]

PMID: 31063988

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Project description:Bariatric surgery is associated with bone loss but skeletal consequences may differ between Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), the two most commonly performed bariatric procedures. Furthermore, severe weight loss is associated with high marrow adipose tissue (MAT); however, MAT is also increased in visceral adiposity. The purpose of our study was to determine the effects of RYGB and SG on BMD and MAT. We hypothesized that both bariatric procedures would lead to a decrease in BMD and MAT. We studied 21 adults with morbid obesity (mean BMI 44.1±5.1kg/m2) prior to and 12months after RYGB (n=11) and SG (n=10). All subjects underwent DXA and QCT of the lumbar spine and hip to assess aBMD and vBMD. Visceral (VAT) and subcutaneous (SAT) adipose tissue was quantified at L1-L2. MAT of the lumbar spine and femur was assessed by 1H-MR spectroscopy. Calcitropic hormones and bone turnover markers were determined. At 12months after surgery, mean weight and abdominal fat loss was similar between the RYGB and SG groups. Mean serum calcium, 25(OH)-vitamin D, and PTH levels were unchanged after surgery and within the normal range in both groups. Bone turnover markers P1NP and CTX increased within both groups and P1NP increased to a greater extent in the RYGB group (p=0.03). There were significant declines from baseline in spine aBMD and vBMD within the RYGB and SG groups, although the changes were not significantly different between groups (p=0.3). Total hip and femoral neck aBMD by DXA decreased to a greater extent in the RYGB than the SG group (p<0.04) although the change in femoral vBMD by QCT was not significantly different between groups (p>0.2). MAT content of the lumbar spine and femoral diaphysis did not change from baseline in the RYGB group but increased after SG (p=0.03). Within the SG group, 12-month change in weight and VAT were positively associated with 12-month change in MAT (p<0.04), suggesting that subjects with less weight and VAT loss had higher MAT. In conclusion, RYGB and SG are associated with declines in lumbar spine BMD, however, the changes are not significantly different between the groups. RYGB may be associated with greater decline of aBMD at the total hip and femoral neck compared to SG. MAT content increased after SG and this was associated with lower weight and VAT loss.

Project description:BackgroundSleeve gastrectomy (SG) is a profoundly effective operation for severe obese patients, but is closely associated with bone mass loss. Previous studies have reported changes of various serum factors which may be associated with bone mass loss after SG. However, those results are contradictory. In this study, we assessed the effects of SG on bone mass, microstructure of femurs, and changes in bone turnover markers (BTMs), serum adipokines, inflammatory factors and gastrointestinal hormones after SG in high-fat diet (HFD) induced obese rats.MethodsEight-week-old male Sprague-Dawley (SD) rats were fed with HFD to induce obesity. Then, SG and sham surgery were performed in anesthetized obese rats. SD rats in control group were fed with standard chow. Microstructure of femurs was scanned and analyzed by micro-computed tomography in control group, HFD sham group and HFD SG group. Serum inflammatory factors, adipokines markers, gastrointestinal hormones and BTMs were also measured.ResultsBone mineral density (BMD) of trabecular bone in both HFD sham group and HFD SG group were remarkably decreased compared with control group. All serum BTMs were significantly higher in HFD SG group than HFD sham group. In the meantime, serum levels of several important inflammatory factors, gastrointestinal hormones and adipokines such as tumor necrosis factor-α (TNF-α), interleukin (IL)-6, monocyte chemoattractant protein-1(MCP-1), ghrelin, insulin and leptin in HFD SG group were remarkably reduced compared with HFD sham group, whereas glucagon-like peptide-1 (GLP-1), adiponectin, fibroblast growth factor (FGF)-19 and FGF-21 were dramatically increased after SG. Protein tyrosine phosphatase 1B (PTP1B) was significantly increased in the HFD sham group than control group. Spearman's correlation analysis indicated that serum osteocalcin (OC) and 25-hydroxy vitamin D3 (25(OH)D3) were positively correlated with BMD of trabecular bone, whereas serum PTP1B and TNF-α were negatively related to BMD of trabecular bone.ConclusionsSG aggravates bone mass loss and activates bone remodeling in obese rats. Levels of BTMs, adipokines, inflammatory factors, and gastrointestinal hormones could be affected by SG in obese rats. Serum PTP1B level might be associated with abnormal bone mass in obese rats.

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G-CSF partially mediates effects of sleeve gastrectomy on the bone marrow niche.

Publications

G-CSF partially mediates effects of sleeve gastrectomy on the bone marrow niche.

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