scholarly journals Soy Protein Isolate Inhibits High-Fat Diet-Induced Senescence Pathways in Osteoblasts to Maintain Bone Acquisition in Male Rats

Endocrinology ◽  
2014 ◽  
Vol 156 (2) ◽  
pp. 475-487 ◽  
Author(s):  
Jin-Ran Chen ◽  
Oxana P. Lazarenko ◽  
Michael L. Blackburn ◽  
Thomas M. Badger ◽  
Martin J. J. Ronis

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, the 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 with those of 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 the p53/p21 signaling pathways. HF-Cas–fed rats had increased caveolin-1 and down-regulated Sirt1, leading to activations of peroxisome proliferator–activated receptor γ (PPARγ) and p53/p21, whereas rats fed HF-SPI suppressed caveolin-1 and activated Sirt1 to deacetylate PPARγ and p53 in bone. Treatment of osteoblastic cells with nonesterified free fatty acid (NEFA) increased cell senescence signaling pathways. Isoflavones significantly blocked activations of senescence-associated β-galactosidase and PPARγ/p53/p21 by NEFA. Finally, replicative senescent osteoblastic cells and bone marrow mesenchymal ST2 cells exhibited behavior similar to that of cells treated with NEFA and in vivo bone cells in rats fed the 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 and (2) the molecular mechanisms underlying the SPI-protective effects involve isoflavone-induced inhibition of osteoblastic cell senescence to prevent HF-induced bone impairments.

Endocrinology ◽  
2015 ◽  
pp. en.0000-9999
Author(s):  
Jin-Ran Chen ◽  
Oxana P. Lazarenko ◽  
Michael L. Blackburn ◽  
Thomas M. Badger ◽  
Martin J. J. Ronis

2014 ◽  
Vol 28 (7) ◽  
pp. 3134-3145 ◽  
Author(s):  
Jian Zhang ◽  
Oxana P. Lazarenko ◽  
Michael L. Blackburn ◽  
Thomas M. Badger ◽  
Martin J. J. Ronis ◽  
...  

2004 ◽  
Vol 134 (12) ◽  
pp. 3270-3276 ◽  
Author(s):  
Martin J. Ronis ◽  
Ying Chen ◽  
Chan-He Jo ◽  
Pippa Simpson ◽  
Thomas M. Badger

2001 ◽  
Vol 166 (1) ◽  
pp. 27-32 ◽  
Author(s):  
Reza Hakkak ◽  
Soheila Korourian ◽  
Martin J.J Ronis ◽  
Jeffery M Johnston ◽  
Thomas M Badger

2017 ◽  
Vol 242 (6) ◽  
pp. 635-644 ◽  
Author(s):  
Kelly E Mercer ◽  
Casey F Pulliam ◽  
Kim B. Pedersen ◽  
Leah Hennings ◽  
Martin JJ Ronis

Alcoholic and nonalcoholic fatty liver diseases are risk factors for development of hepatocellular carcinoma, but the underlying mechanisms are poorly understood. On the other hand, ingestion of soy-containing diets may oppose the development of certain cancers. We previously reported that replacing casein with a soy protein isolate reduced tumor promotion in the livers of mice with alcoholic liver disease after feeding a high fat ethanol liquid diet following initiation with diethylnitrosamine. Feeding soy protein isolate inhibited processes that may contribute to tumor promotion including inflammation, sphingolipid signaling, and Wnt/β-catenin signaling. We have extended these studies to characterize liver tumor promotion in a model of nonalcoholic fatty liver disease produced by chronic feeding of high-fat liquid diets in the absence of ethanol. Mice treated with diethylnitrosamine on postnatal day 14 were fed a high-fat liquid diet made with casein or SPI as the sole protein source for 16 weeks in adulthood. Relative to mice fed normal chow, a high fat/casein diet led to increased tumor promotion, hepatocyte proliferation, steatosis, and inflammation. Replacing casein with soy protein isolate counteracted these effects. The high fat diets also resulted in a general increase in transcripts for Wnt/β-catenin pathway components, which may be an important mechanism, whereby hepatic tumorigenesis is promoted. However, soy protein isolate did not block Wnt signaling in this nonalcoholic fatty liver disease model. We conclude that replacing casein with soy protein isolate blocks development of steatosis, inflammation, and tumor promotion in diethylnitrosamine-treated mice fed high fat diets. Impact statement The impact of dietary components on cancer is a topic of great interest for both the general public and the scientific community. Liver cancer is currently the second leading form of cancer deaths worldwide. Our study has addressed the effect of the protein source on hepatic tumor promotion in a mouse model reflecting aspects of non-alcoholic fatty liver disease (NAFLD). A high-fat liquid diet with casein as the protein source promotes hepatic injury and tumor promotion in diethylnitrosamine-treated mice. Replacing casein with a soy protein isolate led to a pronounced diminishment of tumor promotion and associated hepatic injury and inflammation. The study thus demonstrates that a dietary protein source can have beneficial, preventative effects on hepatic tumor promotion.


2001 ◽  
Vol 20 (3) ◽  
pp. 165-174 ◽  
Author(s):  
Thomas M. Badger ◽  
Martin J. J. Ronis ◽  
Reza Hakkak

Dietary factors other than the traditional nutrients are found in the so-called functional foods. They are becoming increasingly recognized as potentially important for maintaining good health. Soybeans are rich in such factors thought to help prevent certain chronic diseases. Soy protein isolate (SPI) is one of the three major proteins used in infant formulas sold in the United States, with casein (CAS) and whey (WPH) proteins being the others. We have been studying the health effects of these proteins. Safety concerns have developed over the consumption of soy-based infant formula, partly because of the high circulating levels of the total isoflavones (phytoestrogens) during “critical periods of infant development.” There is a paucity of data on developmental, physiological, neurophysiological, behavioral, metabolic, or molecular effects of soy phytochemicals in humans, especially during pregnancy and infancy. We have studied the effects of CAS, SPI, and WPH in short-term, long-term, and multigenerational studies in rats. Aside from minor differences in body weight gain profiles, CAS-, SPI-or WPH-fed rats did not differ in development, organ weights, in vitro hepatic metabolism of testosterone (T), or reproductive performance. However, some endocrine-related functions differed between rats fed these proteins. We found that SPI accelerated puberty in female rats ( p <.05) and WPH delayed puberty in males and females, as compared with CAS ( p <.05). Gender differences were also found in gonadectomy-induced steroid responses. Male rats had normal serum T levels, but female rats fed SPI had reduced serum 17β-estradiol concentrations and a blunted 17β-estradiol response to ovariectomy, as compared to rats fed CAS or WHP ( p <.05). Female rats fed SPI or WHP or treated with genistein had reduced incidence of chemically induced mammary cancers ( p <.05) compared to CAS controls, with WHP reducing tumor incidence by as much as 50%, findings that replicate previous results from our laboratory. Together, these results suggest gender-specific differences in development and certain endocrine responses among rats fed diets composed of a single protein source such as those used in infant formulas. Whether similar developmental effects occur in human infants is unknown, but unlikely because (1) most infants do not consume such diets throughout life as these rats did, and (2) no such effects have been reported in millions of American infants fed infant formula containing these proteins. The long-term health consequence implications of early diet exposure to SPI and WPH, such as reduced breast cancer incidence, are likely to be very positive.


1999 ◽  
Vol 129 (11) ◽  
pp. 1958-1965 ◽  
Author(s):  
Martin J Ronis ◽  
J. Craig Rowlands ◽  
Reza Hakkak ◽  
Thomas M. Badger

Author(s):  
Elizabeth Dawn Grisley ◽  
Kalene N. Huber ◽  
Austen N. Knapp ◽  
Dustie N. Butteiger ◽  
William J. Banz ◽  
...  

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