p38α function in osteoblasts influences adipose tissue homeostasis.

Area of Science:

• Bone biology
• Metabolic regulation
• Endocrinology

Background:

• The skeleton functions as an endocrine organ, secreting osteocalcin (Oc) and fibroblast growth factor 23 (FGF23) to regulate metabolism and homeostasis.
• Evidence suggests osteoblasts secrete additional factors impacting bone's endocrine role.

Purpose of the Study:

• To identify novel bone-derived factors involved in energy metabolism regulation.
• To investigate the role of p38α MAPK in osteoblast function and its systemic effects.

Main Methods:

• Generated mice with conditional osteoblast-specific deletion of p38α MAPK.
• Assessed body weight, adiposity, caloric intake, and energy expenditure.
• Measured blood levels of neuropeptide Y (NPY), insulin, Oc, and FGF23.
• Analyzed Npy expression in various tissues, including bone and osteoblasts.
• Administered recombinant NPY to assess its effect on adiposity.

Main Results:

• Osteoblast-specific p38α MAPK deletion led to decreased body weight and adiposity.
• Increased energy expenditure and Ucp1 expression in adipose tissues were observed.
• Blood NPY levels significantly decreased, while Oc and FGF23 remained unchanged.
• Npy expression declined specifically in bone and primary osteoblasts.
• Recombinant NPY administration partially restored white adipose tissue (WAT) weight and adipocyte size.

Conclusions:

• Bone-derived neuropeptide Y (NPY) plays a role in regulating energy expenditure and fat metabolism.
• Osteoblast dysfunction, linked to p38α MAPK, impacts systemic energy balance through altered NPY signaling.
• These findings highlight novel bone-derived signals beyond Oc and FGF23 in metabolic regulation.