Insulin Signaling in Bone Marrow Adipocytes

Curr Osteoporos Rep. 2019 Dec;17(6):446-454. doi: 10.1007/s11914-019-00552-8.

Abstract

Purpose of review: The goal of this review is to discuss the role of insulin signaling in bone marrow adipocyte formation, metabolic function, and its contribution to cellular senescence in relation to metabolic bone diseases.

Recent findings: Insulin signaling is an evolutionally conserved signaling pathway that plays a critical role in the regulation of metabolism and longevity. Bone is an insulin-responsive organ that plays a role in whole body energy metabolism. Metabolic disturbances associated with obesity and type 2 diabetes increase a risk of fragility fractures along with increased bone marrow adiposity. In obesity, there is impaired insulin signaling in peripheral tissues leading to insulin resistance. However, insulin signaling is maintained in bone marrow microenvironment leading to hypermetabolic state of bone marrow stromal (skeletal) stem cells associated with accelerated senescence and accumulation of bone marrow adipocytes in obesity. This review summarizes current findings on insulin signaling in bone marrow adipocytes and bone marrow stromal (skeletal) stem cells and its importance for bone and fat metabolism. Moreover, it points out to the existence of differences between bone marrow and peripheral fat metabolism which may be relevant for developing therapeutic strategies for treatment of metabolic bone diseases.

Keywords: Bone marrow adipose tissue; Bone marrow mesenchymal stem cells; Insulin signaling; Marrow adiposity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adipocytes / metabolism*
  • Adipogenesis
  • Adipose Tissue / metabolism
  • Animals
  • Bone Diseases, Metabolic / metabolism*
  • Bone Marrow / metabolism
  • Bone Marrow Cells / metabolism*
  • Bone and Bones / metabolism*
  • Cell Differentiation
  • Cellular Senescence*
  • Glucagon-Like Peptide 1 / metabolism
  • Glucose / metabolism
  • Humans
  • Insulin / metabolism*
  • Insulin Receptor Substrate Proteins / metabolism
  • Insulin Resistance
  • Insulin-Like Growth Factor Binding Protein 4 / metabolism
  • Insulin-Like Growth Factor I / metabolism
  • Mesenchymal Stem Cells / metabolism
  • Obesity / metabolism
  • Parathyroid Hormone / metabolism
  • Receptor for Advanced Glycation End Products / metabolism
  • Receptor, Insulin / metabolism

Substances

  • Insulin
  • Insulin Receptor Substrate Proteins
  • Insulin-Like Growth Factor Binding Protein 4
  • Parathyroid Hormone
  • Receptor for Advanced Glycation End Products
  • Insulin-Like Growth Factor I
  • Glucagon-Like Peptide 1
  • Receptor, Insulin
  • Glucose