Obesity reduces bone density associated with activation of PPARγ and suppression of Wnt/β-catenin in rapidly growing male rats
| Autor: | Kartik Shankar, Yudong Tong, Oxana P. Lazarenko, Michael L. Blackburn, Jin-Ran Chen, Martin J. J. Ronis, Xianli Wu, Thomas M. Badger |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Peak bone mass
Male medicine.medical_specialty Stromal cell Bone density Osteoporosis lcsh:Medicine Growth Bone resorption Cell Biology/Cell Signaling NEFA Bone Density Internal medicine Nutrition/Obesity medicine Animals Obesity lcsh:Science beta Catenin Multidisciplinary Osteoblasts biology lcsh:R food and beverages Cell Differentiation medicine.disease Dietary Fats Rats PPAR gamma Wnt Proteins medicine.anatomical_structure Endocrinology Osteocalcin biology.protein Developmental Biology/Cell Differentiation Parenteral Nutrition Total lcsh:Q Bone marrow Research Article |
| Zdroj: | PLoS ONE, Vol 5, Iss 10, p e13704 (2010) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Background: It is well established that excessive consumption of a high fat diet (HFD) results in obesity; however, the consequences of obesity on postnatal skeletal development have not been well studied. Methodology and Principal Findings: Total enteral nutrition (TEN) was used to feed postnatal day 27 male rats intragastrically with a high 45% fat diet (HFD) for four weeks to induce obesity. Fat mass was increased compared to rats fed TEN diets containing 25% fat (medium fat diet, MFD) or a chow diet (low fat diet, LFD) fed ad libitum with matched body weight gains. Serum leptin and total non-esterified fatty acids (NEFA) were elevated in HFD rats, which also had reduced bone mass compared to LFD-fed animals. This was accompanied by decreases in bone formation, but increases in the bone resorption. Bone marrow adiposity and expression of adipogenic genes, PPARc and aP2 were increased, whereas osteoblastogenic markers osteocalcin and Runx2 were decreased, in bone in HFD rats compared to LFD controls. The diversion of stromal cell differentiation in response to HFD stemmed from down-regulation of the key canonical Wnt signaling molecule b-catenin protein and reciprocal up-regulation of nuclear PPARc expression in bone. In a set of in vitro studies using pluripotent ST2 bone marrow mesenchymal stromal cells treated with serum from rats on the different diets or using the free fatty acid composition of NEFA quantified in rat serum from HFD-fed animals by GC-MS, we were able to recapitulate our in vivo findings. Conclusions/Significance: These observations strongly suggest that increased NEFA in serum from rats made obese by HFD-feeding impaired bone formation due to stimulation of bone marrow adipogenesis. These effects of obesity on bone in early life may result in impaired attainment of peak bone mass and therefore increase the prevalence of osteoporosis later on in life. |
| Databáze: | OpenAIRE |
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