Hepatic lipase is expressed by osteoblasts and modulates bone remodeling in obesity

TY - JOUR

T1 - Hepatic lipase is expressed by osteoblasts and modulates bone remodeling in obesity

AU - Bartelt, Alexander

AU - Beil, Timo

AU - Müller, Brigitte

AU - Koehne, Till

AU - Yorgan, Timur A

AU - Heine, Markus

AU - Yilmaz, Tayfun

AU - Ruether, Wolfgang

AU - Heeren, Joerg

AU - Schinke, Thorsten

AU - Niemeier, Andreas

N1 - Copyright © 2014 Elsevier Inc. All rights reserved.

PY - 2014/5/1

Y1 - 2014/5/1

N2 - A number of unexpected molecules were recently identified as products of osteoblasts, linking bone homeostasis to systemic energy metabolism. Here we identify the lipolytic enzyme hepatic lipase (HL, encoded by Lipc) as a novel cell-autonomous regulator of osteoblast function. In an unbiased genome-wide expression analysis, we find Lipc to be highly induced upon osteoblast differentiation, verified by quantitative Taqman analyses of primary osteoblasts in vitro and of bone samples in vivo. Functionally, loss of HL in vitro leads to increased expression and secretion of osteoprotegerin (OPG), while expression of some osteoblast differentiation makers is impaired. When challenging energy metabolism in a diet-induced obesity (DIO) study, lack of HL leads to a significant increase in bone formation markers and a decrease in bone resorption markers. Accordingly, in the DIO setting, we observe in Lipc(-/-) animals but not in wild-type controls a significant increase in lumbar vertebral trabecular bone mass and formation rate as well as in femoral trabecular bone mass and cortical thickness. Taken together, we demonstrate that HL expressed by osteoblasts has an impact on osteoblast OPG expression and that lack of HL leads to increased bone mass in DIO. These data provide a novel and completely unexpected molecular link in the complex interplay of osteoblasts and systemic energy metabolism.

AB - A number of unexpected molecules were recently identified as products of osteoblasts, linking bone homeostasis to systemic energy metabolism. Here we identify the lipolytic enzyme hepatic lipase (HL, encoded by Lipc) as a novel cell-autonomous regulator of osteoblast function. In an unbiased genome-wide expression analysis, we find Lipc to be highly induced upon osteoblast differentiation, verified by quantitative Taqman analyses of primary osteoblasts in vitro and of bone samples in vivo. Functionally, loss of HL in vitro leads to increased expression and secretion of osteoprotegerin (OPG), while expression of some osteoblast differentiation makers is impaired. When challenging energy metabolism in a diet-induced obesity (DIO) study, lack of HL leads to a significant increase in bone formation markers and a decrease in bone resorption markers. Accordingly, in the DIO setting, we observe in Lipc(-/-) animals but not in wild-type controls a significant increase in lumbar vertebral trabecular bone mass and formation rate as well as in femoral trabecular bone mass and cortical thickness. Taken together, we demonstrate that HL expressed by osteoblasts has an impact on osteoblast OPG expression and that lack of HL leads to increased bone mass in DIO. These data provide a novel and completely unexpected molecular link in the complex interplay of osteoblasts and systemic energy metabolism.

U2 - 10.1016/j.bone.2014.01.001

DO - 10.1016/j.bone.2014.01.001

M3 - SCORING: Journal article

C2 - 24440515

VL - 62

SP - 90

EP - 98

JO - BONE

JF - BONE

SN - 8756-3282

ER -