Soy Isoflavones Prevent Bone Quality Loss Induced by High-Fat Diet in Rats Through Epigenetic Modifications

Area of Science:

• Nutritional Science
• Bone Biology
• Epigenetics

Background:

• High-fat diets (HFDs) induce obesity, insulin resistance, and negatively impact bone metabolism.
• Soy isoflavones (Isofs) are known to benefit connective tissue metabolism.
• The protective effects of soy Isofs on bone development under HFD conditions are not well understood.

Purpose of the Study:

• To investigate the effects of soy isoflavone (Isof) supplementation on bone development, morphology, and remodeling in rats fed a high-fat diet (HFD).
• To explore the potential molecular mechanisms, including epigenetic modifications, underlying Isof's bone-protective effects.

Main Methods:

• Male Sprague-Dawley rats were fed either a control diet or an HFD with or without soy Isof supplementation for 8 weeks.
• Bone mass, morphology, and strength were assessed using micro-CT and three-point bending tests.
• Serum markers, gene expression (Ezh2, NFATc1), and epigenetic modifications (H3K27me3, DNA methylation) were analyzed.

Main Results:

• HFD consumption led to increased body weight, bone length, adiposity, and insulin resistance.
• Soy Isof supplementation prevented HFD-induced reductions in bone mass and strength.
• Isofs decreased non-esterified free fatty acid (NEFA) levels, ameliorated HFD-induced increases in Ezh2 and H3K27me3, and blocked osteoclastic marker expression.
• Isof supplementation inhibited HFD-induced increases in bone DNA methylation and correlated with reduced NEFA and Ezh2 expression.

Conclusions:

• HFD disrupts bone and adipose tissue development and remodeling in juvenile rats.
• Dietary soy Isofs protect against HFD-induced bone impairments.
• Isof's protective mechanisms may involve the modulation of histone and DNA methylation via Ezh2 regulation.