Chinese Journal of Tissue Engineering Research ›› 2026, Vol. 30 ›› Issue (12): 3100-3108.doi: 10.12307/2026.736

Previous Articles     Next Articles

Regulatory mechanism of leptin in bone metabolism

Sun Long1, Wu Haiyang2, Tong Linjian3, Liu Rui3, Yang Weiguang4, Xiao Jian5, Liu Lice6, Sun Zhiming7   

  1. 1Class 2024 MS Candidate, 5Class 2022 MS Candidate, 6Class 2023 MS Candidate, Tianjin Medical University, Tianjin 300170, China; 2Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450047, Henan Province, China; 3Tianjin Huanhu Hospital, Affiliated Hospital of Tianjin Medical University, Tianjin 300350, China; 4Tianjin Medical University General Hospital, Tianjin 300052, China; 7Tianjin Third Central Hospital/Tianjin University Central Hospital, Tianjin 300170, China
  • Received:2025-07-09 Accepted:2025-08-30 Online:2026-04-28 Published:2025-09-30
  • Contact: Sun Zhiming, Chief physician, Professor, Doctoral supervisor, Tianjin Third Central Hospital/Tianjin University Central Hospital, Tianjin 300170, China
  • About author:Sun Long, MS candidate, Class 2024 MS Candidate, Tianjin Medical University, Tianjin 300170, China
  • Supported by:
    Tianjin Natural Science Foundation (General Program), No. 23JCYBJC01740 (to SZM)

Abstract: BACKGROUND: Recent studies have revealed that leptin participates in bone metabolism regulation through complex multidimensional mechanisms involving the central nervous system, peripheral direct actions, and the “gut-bone axis.” 
OBJECTIVE: To systemically review the latest research advances in leptin-mediated bone metabolism regulation.
METHODS: A systematic literature search was conducted in databases including PubMed and CNKI, covering publications up to April 2025. The search terms included “leptin, leptin receptor, bone metabolism, osteoblasts, osteoclasts, gut microbiota, osteoporosis” in English and Chinese, respectively. According to the inclusion criteria, a total of 80 articles were included for review.
RESULTS AND CONCLUSION: Leptin directly promotes osteogenic differentiation of bone marrow mesenchymal stem cells while inhibiting adipogenesis, a process closely linked to vitamin D metabolism. The newly identified second ligand of the leptin receptor, angiopoietin-like protein 4, drives heterotopic ossification, explaining the unique phenotypes observed in leptin receptor mutation models. Histone deacetylase 6 enhances leptin sensitivity by modulating receptor acetylation. Gut microbiota regulates leptin levels via short-chain fatty acids, and fecal microbiota transplantation from young donors increases bone mass in aged osteoporotic models. Leptin exhibits distinct central and peripheral effects: it inhibits trabecular bone formation via the hypothalamus while directly promoting cortical bone mineralization. These discoveries provide novel insights for developing multi-system therapeutic strategies targeting the “gut-brain-bone” axis. Future research should focus on resolving key challenges such as leptin resistance mechanisms and central delivery efficiency to advance precision medicine for metabolic bone diseases.

Key words: leptin, leptin receptor, bone metabolism, osteoblasts, osteoclasts, gut microbiota, osteoporosis

CLC Number: