RANKL induces beige adipocyte differentiation in preadipocytes

Area of Science:

• Endocrinology
• Metabolic Regulation
• Adipose Tissue Biology

Background:

• The receptor activator of nuclear factor-κB (RANK), its ligand (RANKL), and osteoprotegerin (OPG) are key regulators of bone metabolism.
• Serum OPG is a biomarker for cardiovascular diseases and Type 2 diabetes.
• The role of OPG in adipose tissue metabolism is largely unknown.

Purpose of the Study:

• To investigate the role of RANK-RANKL-OPG signaling in white adipose tissue browning.
• To explore the impact of OPG deficiency on metabolic parameters and adipose tissue characteristics.
• To determine the effect of RANKL on adipocyte differentiation and energy expenditure.

Main Methods:

• Histological analysis of osteoprotegerin knockout (OPG-/-) mice and wild-type (WT) controls.
• Analysis of stromal vascular fraction (SVF) cells from subcutaneous white adipose tissue (sWAT).
• Indirect calorimetry to measure oxygen consumption and respiratory rates.
• In vitro differentiation assays using SVF cells and 3T3-L1 cells with RANKL stimulation.

Main Results:

• OPG-/- mice displayed sWAT browning, resistance to high-fat diet-induced weight gain, and preserved glucose metabolism compared to WT mice.
• SVF cells from OPG-/- mice showed multilocular morphology and increased expression of brown adipocyte markers.
• RANKL infusion induced sWAT browning, elevated respiratory rates, and increased whole-body oxygen consumption.
• RANKL stimulated the differentiation of sWAT-derived SVF and 3T3-L1 cells into beige adipocytes, characterized by multilocular lipid droplets and altered lipid content.

Conclusions:

• RANKL contributes to increased energy expenditure by inducing beige adipocyte differentiation in preadipocytes.
• OPG deficiency promotes white adipose tissue browning and improves metabolic health.
• The RANK-RANKL-OPG system plays a significant role in regulating adipose tissue metabolism and energy balance.