The PYY/Y2R-deficient male mouse is not protected from bone loss due to Roux-en-Y gastric bypass.

Autor: Zahedi B; Endocrine Unit, Massachusetts General Hospital, Boston, MA 02114, United States of America. Electronic address: bzahedi@partners.org., Daley EJ; Endocrine Unit, Massachusetts General Hospital, Boston, MA 02114, United States of America., Brooks DJ; Endocrine Unit, Massachusetts General Hospital, Boston, MA 02114, United States of America., Bruce M; Endocrine Unit, Massachusetts General Hospital, Boston, MA 02114, United States of America., Townsend RL; Neurobiology of Nutrition & Metabolism Department, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA 70808, United States of America., Berthoud HR; Neurobiology of Nutrition & Metabolism Department, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA 70808, United States of America., Bouxsein ML; Endocrine Unit, Massachusetts General Hospital, Boston, MA 02114, United States of America., Yu EW; Endocrine Unit, Massachusetts General Hospital, Boston, MA 02114, United States of America.
Jazyk: angličtina
Zdroj: Bone [Bone] 2023 Feb; Vol. 167, pp. 116608. Date of Electronic Publication: 2022 Nov 08.
DOI: 10.1016/j.bone.2022.116608
Abstrakt: Background: Peptide YY (PYY) is an anorexigenic gut hormone that also has anti-osteogenic effects, inhibiting osteoblastic activity and inducing catabolic effects. It has been postulated that increases in PYY after Roux-en-Y gastric bypass (RYGB) contribute to declines in bone mineral density (BMD) and increases in bone turnover. The aim of this study is to determine the role of the PYY Y2-receptor in mediating bone loss post-RYGB in mice.
Methods: We compared adult male wildtype (WT) and PYY Y2 receptor-deficient (KO) C57BL/6 mice that received RYGB (WT: n = 8; KO: n = 9), with sham-operated mice (Sham; WT: n = 9; KO: n = 10) and mice that were food-restricted to match the weights of the RYGB-treated group (Weight-Matched, WM; WT: n = 7; KO: n = 5). RYGB or sham surgery was performed at 15-16 weeks of age, and mice sacrificed 21 weeks later. We characterized bone microarchitecture with micro-computed tomography (μCT) at the distal femur (trabecular) and femoral midshaft (cortical). Differences in body weight, bone microarchitecture and biochemical bone markers (parathyroid hormone, PTH; C-telopeptide, CTX; and type 1 procollagen, P1NP) were compared using 2-factor ANOVA with Tukey's adjustments for multiple comparisons.
Results: Body weights were similar in the WT-RYGB, WT-WM, KO-RYGB, and KO-WM: 41-44 g; these groups weighed significantly less than the Sham surgery groups: 55-57 g. Trabecular BMD was 31-43 % lower in RYGB mice than either Sham or WM in WT and KO groups. This deficiency in trabecular bone was accompanied by a lower trabecular number (19 %-23 %), thickness (22 %-30 %) and increased trabecular spacing (25 %-34 %) in WT and KO groups (p < 0.001 for all comparisons vs. RYGB). RYGB led to lower cortical thickness, cortical tissue mineral density, and cortical bone area fraction as compared to Sham and WM in WT and KO groups (p ≤ 0.004 for all). There were no interactions between genotype and bone microarchitecture, with patterns of response to RYGB similar in both WT and KO groups. CTX and P1NP were significantly higher in RYGB mice than WM in WT and KO groups. PTH did not differ among groups.
Conclusions: RYGB induced greater trabecular and cortical deficits and high bone turnover than observed in weight-matched mice, with a similar pattern in the WT and Y2RKO mice. Thus, skeletal effects of RYGB are independent of weight loss, and furthermore, PYY signaling through Y2R is not a key mediator of bone loss post-RYGB.
Competing Interests: Declaration of competing interest EWY has received a research grant to the Massachusetts General Hospital from Amgen for unrelated studies. Other authors have nothing to disclose.
(Copyright © 2022 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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