J Bone Metab.  2017 Feb;24(1):1-8. 10.11005/jbm.2017.24.1.1.

Role of the Cytokine-like Hormone Leptin in Muscle-bone Crosstalk with Aging

• Hamrick MW

• KMID: 2371826
• DOI: http://doi.org/10.11005/jbm.2017.24.1.1

Abstract

The cytokine-like hormone leptin is a classic adipokine that is secreted by adipocytes, increases with weight gain, and decreases with weight loss. Additional studies have, however, shown that leptin is also produced by skeletal muscle, and leptin receptors are abundant in both skeletal muscle and bone-derived mesenchymal (stromal) stem cells. These findings suggest that leptin may play an important role in muscle-bone crosstalk. Leptin treatment in vitro increases the expression of myogenic genes in primary myoblasts, and leptin treatment in vivo increases the expression of microRNAs involved in myogenesis. Bone marrow adipogenesis is associated with low bone mass in humans and rodents, and leptin can reduce marrow adipogenesis centrally through its receptors in the hypothalamus as well as directly via its receptors in bone marrow stem cells. Yet, central leptin resistance can increase with age, and low circulating levels of leptin have been observed among the frail elderly. Thus, aging appears to significantly alter leptin-mediated crosstalk among various organs and tissues. Aging is associated with bone loss and muscle atrophy, contributing to frailty, postural instability, and the incidence of falls. Therapeutic interventions such as protein and amino acid supplementation that can increase muscle mass and muscle-derived leptin may have multiple benefits for the elderly that can potentially reduce the incidence of falls and fractures.

Keyword

Insulin-like growth factor I; Leptin; Mesenchymal stromal cells; Osteoporosis; Sarcopenia

MeSH Terms

Accidental Falls
Adipocytes
Adipogenesis
Adipokines
Aged
Aging*
Bone Marrow
Frail Elderly
Humans
Hypothalamus
In Vitro Techniques
Incidence
Insulin-Like Growth Factor I
Leptin*
Mesenchymal Stromal Cells
MicroRNAs
Muscle Development
Muscle, Skeletal
Muscular Atrophy
Myoblasts
Osteoporosis
Receptors, Leptin
Rodentia
Sarcopenia
Stem Cells
Weight Gain
Weight Loss
Adipokines
Insulin-Like Growth Factor I
Leptin
MicroRNAs
Receptors, Leptin

Figure

• 

  Fig. 1 (A) Leptin levels measured in homogenized mouse tissue normalized by total protein. Means with different superscripts differ significantly from one another (P<0.05). (B) Immunostaining for the long form of the leptin receptor (Ob-R) in cross-sections of mouse skeletal muscle, showing positive staining relative to control samples (no primary antibody). (C) Peripheral, direct (muscle) and central (hypothalamic) pathways through which leptin alters pathways regulating skeletal muscle hypertrophy. (D) Leptin levels measured in homogenized mouse tissue normalized by total protein in young adult (12 months) and aged (12 months) mouse samples. ns, not statistically significant (P<0.05) for age-related differences; GH, growth hormone; IGF, insulin-like growth factor; mTOR, mechanistic target of rapamycin.

• 

  Fig. 2 (A) Immunostaining for the long form of the leptin receptor (Ob-R) in cross-sections of mouse cortical bone (c), showing positive staining in periosteal cells (p) relative to control samples (no primary antibody). (B) Increased number of bone marrow adipocytes (asterisks) in bone cross-sections from POUND mice lacking both forms of the leptin receptor (lb/lb) compared to marrow from normal lean mice. (C) Peripheral, direct (bone-derived mesenchymal stromal cells [BMSC]) and central (hypothalamic) pathways through which leptin alters pathways regulating osteogenesis and adipogenesis in bone marrow. beta-AR, beta-adrenergic receptor.

• 

  Fig. 3 Proposed interactions among dietary protein, muscle-derived leptin, insulin-like growth factor 1 (IGF-1) and muscle mass. Protein and amino acid supplementation is suggested to increase muscle-derived leptin and IGF-1, increasing muscle mass and strength and reducing the risk of falls and fractures.

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