Associations between Postprandial Gut Hormones and Markers of Bone Remodeling.

Nina Jensen,Jonas Quist,Hanne Pedersen,Kim Clemmensen,Joachim Størling,Lars Diaz,Kristine Færch,Marie Jensen

doi:10.3390/nu13093197

Abstract

Gut-derived hormones have been suggested to play a role in bone homeostasis following food intake, although the associations are highly complex and not fully understood. In a randomized, two-day cross-over study on 14 healthy individuals, we performed postprandial time-course studies to examine the associations of the bone remodeling markers carboxyl-terminal collagen type I crosslinks (CTX) and procollagen type 1 N-terminal propeptide (P1NP) with the gut hormones glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP-1), and peptide YY (PYY) using two different meal types—a standardized mixed meal (498 kcal) or a granola bar (260 kcal). Plasma concentrations of total GIP, total GLP-1, total PYY, CTX, and P1NP were measured up to 240 min after meal intake, and the incremental area under the curve (iAUC) for each marker was calculated. The iAUC of CTX and P1NP were used to assess associations with the iAUC of GIP, GLP-1, and PYY in linear mixed effect models adjusted for meal type. CTX was positively associated with GIP and GLP-1, and it was inversely associated with PYY (all p < 0.001). No associations of P1NP with GIP or GLP-1 and PYY were found. In conclusion, the postprandial responses of the gut hormones GIP, GLP-1, and PYY are associated with the bone resorption marker CTX, supporting a link between gut hormones and bone homeostasis following food intake.

Highlights

Bone remodeling is a highly dynamic process that takes place throughout life and helps maintain the skeleton [1]
Carboxyl-terminal collagen type I crosslinks (CTX) is an indicator of bone resorption, where osteoclasts breaks down the bone tissue, whereas procollagen type 1 N-terminal propeptide (P1NP) is an indicator of bone formation, where osteoblasts build up the bone tissue [3,4]
In linear mixed effect models adjusted for meal type, we investigated associations between the incremental area under the curve (iAUC)’s of the two outcomes, CTX and P1NP, and the three gut hormones glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP-1), and Peptide YY (PYY)

Summary

Introduction

Bone remodeling is a highly dynamic process that takes place throughout life and helps maintain the skeleton [1]. The bone remodeling marker levels change acutely following food intake, where CTX is reduced and P1NP is increased, reflecting increased bone formation [7,8]. Recent studies have shown that the intravenous infusion of GIP acutely decreases CTX plasma levels, which is suggestive of increased bone formation [12,13]. Treatment with the GLP-1 receptor agonist liraglutide has been shown to increase P1NP levels and to maintain bone mineral density in obese women after weight loss, suggesting a positive effect of GLP-1 on bone formation [14]. The appetite-inhibiting hormone Peptide YY (PYY) is co-secreted postprandially from the intestinal L-cells with GLP-1/2 and is believed to mainly have bone resorptive effects [6]. Gut hormones seem to represent an important link between food intake and bone homeostasis; the complexity of the associations between different gut hormones and bone turnover markers following food intake remains elusive

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