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ARS Home » Southeast Area » Little Rock, Arkansas » Microbiome and Metabolism Research Unit » Research » Publications at this Location » Publication #319537
Title: Soy protein isolate inhibits high-Ffat diet-induced senescence pathways in osteoblasts to maintain bone acquisition in male rats

Author
item CHEN, JINRAN - Arkansas Children'S Nutrition Research Center (ACNC)
item LAZARENDO, OXANA - Arkansas Children'S Nutrition Research Center (ACNC)
item BLACKBURN, MICHAEL - Arkansas Children'S Nutrition Research Center (ACNC)
item BADGER, THOMAS - Arkansas Children'S Nutrition Research Center (ACNC)
item RONIS, MARTIN - Arkansas Children'S Nutrition Research Center (ACNC)

Submitted to: Endocrinology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/4/2014
Publication Date: 2/8/2015
Citation: Chen, J., Lazarendo, O.P., Blackburn, M.L., Badger, T.M., Ronis, M.J. 2015. Soy protein isolate inhibits high-Ffat diet-induced senescence pathways in osteoblasts to maintain bone acquisition in male rats. Endocrinology. 156(2):475-487.

Interpretive Summary: Excessive taking of a diet containing high in fat and cholesterol during childhood (or adulthood) is known to result in obesity, insulin resistance and other metabolic syndromes. However, the effects of such a high fat diet [usually we refer to “Western diet” (WD)] on bone development and new bone formation is poorly understood. In the current study, we show that young rapidly growing rats fed a WD containing 45% fat and 0.5% cholesterol for 6 weeks starting from 21 days old of age display obesity, and reduced bone quality and quantity (decreased bone mineral density and strength) (BMD). Substitution of dietary casein protein 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 increased activity of osteoblasts, known as bone forming cells in the body. WD significantly increased skeletal ageing, and SPI was able to prevent it. A mixture of free fatty acids (individual acid ratio and concentration similar to their appearance in WD rat serum) decreased activity of osteoblasts. An artificial phytoestrogen mixture (concentrations identical to that found in SPI diet serum) increased osteoblast activity. These results suggest that the protective effects of the SPI diet on the skeleton after WD feeding are due to suppression of serum free fatty acids to preserve osteoblast activity in bone.

Technical Abstract: Chronic consumption by experimental animals of a typical Western diet high in saturated fats and cholesterol during postnatal life has been demonstrated to impair skeletal development. However, underlying mechanism by which high fat, energy dense diets affect bone forming cell phenotypes is poorly understood. Here, we show that male weanling rats fed a diet containing 45% fat and 0.5% cholesterol made with casein (HF-Cas) for 6 weeks displayed lower bone mineral density and strength compared to AIN-93G-fed dietary controls. Substitution of casein with soy protein isolate (SPI) in the high fat diet (HF-SPI) prevented these effects. The bone sparing effects of SPI were associated with prevention of HF-Cas-induced osteoblast senescence pathways through suppression of p53/p21 signaling pathways. HF-Cas-fed rats had increased caveolin-1 and down-regulated Sirt1 leading to activations of PPAR' and p53/p21; whereas, rats fed HF-SPI suppressed caveolin-1and activated Sirt1 to de-acetylate PPAR gamma and p53 in bone. Treatment of osteoblastic cells with non-esterified free fatty acid (NEFA) increased cell senescence signaling pathways. Isoflavones significantly blocked activations of senescence-associated Beta-galactosidase and PPAR gamma/p53/p21 by NEFA. Finally, replicative senescent osteoblastic cells and bone marrow mesenchymal ST2 cells exhibited similar behavior to cells treated with NEFA and in vivo bone cells in rats fed HF-Cas diet. These results suggest that: 1) high concentrations of NEFA occurring with HF intake are mediators of osteoblast cell senescence leading to impairment of bone development and acquisition; 2) the molecular mechanisms underlying the SPI-protective effects involve isoflavone-induced inhibition of osteoblastic cell senescence to prevent HF-induced bone impairments.