|CHEN, JINRAN - Arkansas Children'S Nutrition Research Center (ACNC)|
|ZHANG, JIAN - Arkansas Children'S Nutrition Research Center (ACNC)|
|LAZARENKO, OXANA - Arkansas Children'S Nutrition Research Center (ACNC)|
|RONIS, MARTIN - Arkansas Children'S Nutrition Research Center (ACNC)|
Submitted to: Journal of Bone and Mineral Research
Publication Type: Abstract Only
Publication Acceptance Date: 7/1/2012
Publication Date: 1/10/2013
Citation: Chen, J., Zhang, J., Lazarenko, O.P., Badger, T.M., Ronis, M.J. 2013. Skeletal effects of obesity are prevented by a diet containing soy protein isolate via preservation of insulin signaling in bone [abstract]. Journal of Bone and Mineral Research. 27(Issue Supplement 1):http://www.asbmr.org/Meetings/PastAnnualMeetings.aspx.
Technical Abstract: In both rodents and humans, excessive consumption of diets high in saturated fat and cholesterol during postnatal life is known to result in global energy imbalance, obesity, and insulin resistance. However, the effects of such a "Western diet" (WD) on bone development and remodeling is poorly understood. In the current study, we show that weanling rats fed a WD containing 45% fat and 0.5% cholesterol for 6 weeks starting from postnatal day 21 display obesity, reduced bone mineral density (BMD), significant increase in bone marrow adiposity, insulin resistance, and impaired glucose tolerance. Substitution of dietary casein by soy protein isolate (SPI) is able to block these effects of WD in male rats. Protection of bone by dietary SPI was associated with reduced osteoblast senescence, increased undercarboxylated osteocalcin secretion, and preservation of IRS1/Akt insulin signaling in osteoblasts. While WD significantly increased non-esterified free fatty acid (NEFA) levels in the rat serum, SPI was able to prevent this increase. A mixture of NEFA (individual NEFA ratio and concentration similar to their appearance in WD rat serum) accelerates entrance of osteoblasts or mesenchymal stromal ST2 cells into the senescence pathway and decreased insulin signaling. An artificial isoflavone mixture (concentrations identical to that found in SPI diet serum) increased osteoblast proliferation and blocked activation of p21/p53 and senescence associated beta-galactosidase senescence pathway and insulin resistance that occurred in osteoblasts in response to NEFA. Finally, we show that senescent osteoblastic cells in vitro exhibit phenotypes with reduced ability to secrete osteocalcin and decreased responsiveness to insulin/IGF1 stimulation of cell proliferation and differentiation due to cellular insulin resistance. These results suggest that the protective effects of the SPI diet on the skeleton after WD feeding are due to suppression of serum NEFA and isoflavone-mediated amelioration of osteoblastic cell senescence, increased secretion of osteocalcin, and preservation of insulin signaling in bone.