title: Wnt/β-catenin signaling in osteoblasts regulates global energy metabolism.
abstract: Obesity, diabetes and osteoporosis have become a major public heath burden, and understanding the underlying mechanisms of these pathophysiological process will benefit their treatment. Osteoblast lineage cells in charge of the bone formation have been showed to participate in the whole-body energy metabolism. In this study, we identify that wnt/β-catenin signaling in osteoblasts could regulate global energy metabolism, including glucose homeostasis, fat accumulation and energy expenditure. Mice lacking β-catenin specifically in osteoblasts postnatally exhibit decreased bone mass, increased glucose level, decreased insulin production, decreased fat accumulation and increased energy expenditure. Osteocalcin supplement can rescue the impaired glucose balance by improving insulin production but cannot influence the abnormal fat accumulation and energy expenditure. Osteoprotegerin (OPG) overexpression exclusively in osteoblasts in β-catenin deletion mice can normalize not only the decreased bone mass but also the decreased fat accumulation and increased energy expenditure. The effect of β-catenin deletion and OPG overexpression in osteoblasts on global energy metabolism had no relation with inguinal fat browning. These results suggest that the regulation of bone on energy metabolism and fat accumulation is not mediated exclusively by osteocalcin. Our findings may provide a new insight into the regulation of bone on fat accumulation and energy metabolism.
authors.affiliation: Department of Endocrinology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Yao
authors.affiliation: Department of Endocrinology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.
authors.forename: Caixia
authors.initials: C
authors.lastname: Yu
authors.affiliation: Department of Endocrinology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.
authors.forename: Xiuzhen
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.
authors.forename: Keqin
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Endocrinology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China. Electronic address: 6songlige@tongji.edu.cn.
authors.forename: Lige
authors.initials: L
authors.lastname: Song
mesh_terms: D002001:Adipose Tissue, Brown / Q000473:pathology; D050154:Adiposity; D000818:Animals; D001842:Bone and Bones / Q000473:pathology; D004734:Energy Metabolism; D018149:Glucose Intolerance / Q000378:metabolism / Q000473:pathology; D006706:Homeostasis; D007328:Insulin / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009929:Organ Size; D010006:Osteoblasts / Q000378:metabolism*; D015675:Osteocalcin / Q000378:metabolism; D053244:Osteoprotegerin / Q000378:metabolism; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism
chemical_list: D007328:Insulin; D053244:Osteoprotegerin; D051176:beta Catenin; D015675:Osteocalcin
keywords: Body fat; Glucose; Osteoblast; Osteocalcin; Osteoprotegerin