Bioactives in Inflammation, Intestinal Health, Glucose and Bone Metabolism (Poster Theater Flash Session 4)

(PTFS04-07-25) Soy Isoflavones Prevent Loss of Bone Quality Associated With High Fat Diet in Rats Through Ameliorating Epigenetic Modifications in Bone

Sunday, June 1, 2025

10:24 AM – 10:28 AM ET

Location: South Hall B (The Hub) - Poster Theater / Poster Board Number PT-7

Presenting Author(s)

JC

Jin-Ran Chen, Phd

Associate Professor
Arkansas Children's Nutrition Center / University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States

Disclosure information not submitted.

Co-Author(s)

PC

Perry Caviness, n/a

Postdoctoral Researcher
Arkansas Children's Nutrition Center
LITTLE ROCK, Arkansas, United States
BB

Beau Belcher

Arkansas Children's Nutrition Center
Little Rock, Arkansas, United States
OL

Oxana Lazarenko

Arkansas Children's Nutrition Center
LITTLE ROCK, Arkansas, United States
JC

Jennifer Chen

University of Arkansas
Fayetteville, Arkansas, United States
MB

Michael Blackburn, Phd

Arkansas Children's Nutrition Center / University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States

Objectives: In addition to obesity, chronic consumption of a western style diet high in saturated fats and cholesterol can result in disruption of energy metabolism in bone tissue leading to impaired bone quality. However, isoflavone-rich dietary soy can have beneficial effects on bone tissue metabolism. In this study, the effects of isoflavone dietary supplementation of a high fat diet (HFD) on bone development, morphology and remodeling will be investigated in a rat model.

Methods: Male weanling rats were fed either a AIN-93G diet (Control) or a HFD containing (45% fat by calories) (+/- soy isoflavones, 20 mg Novasoy/kg/d). After 8 weeks rats were sacrificed with serum and bone tissue collected. µCT (SkyScan 1272) and 3-point bending analysis (XForceP 0.2 KN load cell) were used to evaluate changes in bone quality and strength. von Kossa and TRAP staining was performed on decalcified tibia slides (Nikon Eclipse T/2). Levels of bone tissue 5-methylcytosine (%5-mC), a marker of DNA methylation, were determined using ELISA (MethylFlash Global DNA Methylation, EpiGentek).

Results: Rats fed HFD displayed significant increases in body weight and insulin resistance. µCT and 3-point bending analysis revealed that soy isoflavones prevented HFD-induced decreases in bone quality and strength. In addition, isoflavones suppressed HFD-induced effects on TRAP⁺ cell number and non-esterified free fatty acid (NEFA) concentration. Isoflavone supplementation suppressed expression of Ezh2, a histone methyltransferase involved in decreasing bone formation. In addition, isoflavones suppressed HFD-induced increases in %5-mC. Finally, a significant inverse relationship between bone mineral density (BMD) and %5-mC as well as significant positive correlations between serum NEFA level and Ezh2 expression were observed.

Conclusions: Postnatal early life HFD-feeding disrupts bone tissue development and diets high in soy isoflavones may prevent HFD-induced bone impairments through ameliorating increased histone and DNA methylation. Results are necessary for the development dietary intervention strategies to combat effects of chronic HFD on bone development.

Funding Sources: This work was supported in part by United States Department of Agriculture (USDA) / Agricultural Research Service (ARS) CRIS 6251-51000-003 to the Arkansas Children’s Nutrition Center.