A high‑fat diet induces obesity and impairs bone acquisition in young male mice

Lu,Xiao‑Mei; Zhao,Hong; Wang,En‑Hua

doi:10.3892/mmr.2013.1297

A high‑fat diet induces obesity and impairs bone acquisition in young male mice

Authors:
- Xiao‑Mei Lu
- Hong Zhao
- En‑Hua Wang
View Affiliations

Affiliations: Department of Pathophysiology, College of Basic Medicine, China Medical University, Shenyang, Liaoning 110001, P.R. China, Institute of Pathology and Pathophysiology, China Medical University, Shenyang, Liaoning 110001, P.R. China
Published online on: January 29, 2013 https://doi.org/10.3892/mmr.2013.1297
Pages: 1203-1208

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The postnatal development of obesity is highly associated with the excessive consumption of a high‑calorie, high‑fat diet (HFD). However, the correlation between HFD‑induced pediatric obesity and skeletal development remains to be elucidated. In the present study, postnatal day 17 (PND17) mice were weaned on a HFD for eight weeks ad libitum to induce obesity. The HFD mice showed a significant increase in the total body weight and gonadal and abdominal fat mass compared with the control animals. Peripheral quantitative (pQ) CT scans of the tibial bone revealed that the bone mineral density (BMD), including the total, trabecular and cortical BMD, was unchanged between the HFD and control diet groups, but that it was inversely associated with body fat. By contrast, the bone mineral content (BMC) and trabecular area were significantly decreased in the HFD group compared with the control. RNA and protein were isolated from the femur. qPCR and western blot analyses showed a significant downregulation in the gene expression of the key canonical Wnt signaling molecule β‑catenin, the osteoblastic cell differentiation marker Runt‑related transcription factor 2 (Runx2) and also in the β‑catenin gene encoded protein levels of the HFD mice when compared with the controls. Consistent with the increased fat mass in the HFD‑induced obese animals, the expression of the adipogenic genes and aP2 was increased compared with the controls. Bone marrow cells were aspirated and the ex vivo bone marrow cell cultures showed that the number of colony‑forming unit osteoblasts (CFU‑OBs) per bone was significantly decreased in the samples from the HFD mice compared with those from the controls. These observations suggested that HFD‑induced obesity in growing animals may affect the total available osteoblastic cell differentiation progenitors in the bone, while increasing adipogenesis. This may result in negative consequences for the bone later on in adult life.

View Figures

View References

1	Faeh D, Braun J, Tarnutzer S and Bopp M: Obesity but not overweight is associated with increased mortality risk. Eur J Epidemiol. 26:647–655. 2011. View Article : Google Scholar : PubMed/NCBI
2	Ritchie LD, Ivey SL, Woodward-Lopez G and Crawford PB: Alarming trends in pediatric overweight in the United States. Soz Preventivmed. 48:168–177. 2003. View Article : Google Scholar : PubMed/NCBI
3	Weiler HA, Janzen L, Green K, Grabowski J, Seshia MM and Yuen KC: Percentage body fat and bone mass in healthy Canadian females 10 to 19 years of age. Bone. 27:203–207. 2000.PubMed/NCBI
4	Taylor ED, Theim KR, Mirch MC, et al: Orthopedic complications of overweight in children and adolescents. Pediatrics. 117:2167–2174. 2006. View Article : Google Scholar : PubMed/NCBI
5	Zhao LJ, Liu YJ, Liu PY, Hamilton J, Recker RR and Deng HW: Relationship of obesity with osteoporosis. J Clin Endocrinol Metab. 92:1640–1646. 2007. View Article : Google Scholar : PubMed/NCBI
6	Reinwald S and Weaver CM: Soy isoflavones and bone health: a double-edged sword? J Nat Prod. 69:450–459. 2006. View Article : Google Scholar : PubMed/NCBI
7	Reid IR: Relationships among body mass, its components and bone. Bone. 31:547–555. 2002.PubMed/NCBI
8	Leonard MB, Shults J, Wilson BA, Tershakovec AM and Zemel BS: Obesity during childhood and adolescence augments bone mass and bone dimensions. Am J Clin Nutr. 80:514–523. 2004.PubMed/NCBI
9	Zhao LJ, Jiang H, Papasian CJ, Maulik D, Drees B, Hamilton J and Deng HW: Correlation of obesity and osteoporosis: effect of fat mass on the determination of osteoporosis. J Bone Miner Res. 23:17–29. 2008. View Article : Google Scholar : PubMed/NCBI
10	Cao JJ, Gregoire BR and Gao H: High-fat diet decreases cancellous bone mass but has no effect on cortical bone mass in the tibia in mice. Bone. 44:1097–1104. 2009. View Article : Google Scholar : PubMed/NCBI
11	Chan G and Chen CT: Musculoskeletal effects of obesity. Curr Opin Pediatr. 21:65–70. 2009. View Article : Google Scholar
12	Krishnan V, Bryant HU and MacDougald OA: Regulation of bone mass by Wnt signaling. J Clin Invest. 116:1202–1209. 2006. View Article : Google Scholar : PubMed/NCBI
13	Smas CM, Chen L, Zhao L, Latasa MJ and Sul HS: Transcriptional repression of pref-1 by glucocorticoids promotes 3T3-L1 adipocyte differentiation. J Biol Chem. 274:12632–12641. 1999. View Article : Google Scholar : PubMed/NCBI
14	Reeves PG, Nielsen FH and Fahey GC Jr: AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet. J Nutr. 123:1939–1951. 1993.PubMed/NCBI
15	Chen JR, Lazarenko OP, Wu X, et al: Obesity reduces bone density associated with activation of PPARγ and suppression of Wnt/β-catenin in rapidly growing male rats. PLoS One. 5:e137042010.PubMed/NCBI
16	Chen JR, Lazarenko OP, Wu X, et al: Dietary-induced serum phenolic acids promote bone growth via p38 MAPK/β-catenin canonical Wnt signaling. J Bone Miner Res. 25:2399–2411. 2010.PubMed/NCBI
17	Di Gregorio GB, Yamamoto M, Ali AA, Abe E, Roberson P, Manolagas SC and Jilka RL: Attenuation of the self-renewal of transit-amplifying osteoblast progenitors in the murine bone marrow by 17 beta-estradiol. J Clin Invest. 107:803–812. 2001.PubMed/NCBI
18	Chen JR, Lazarenko OP, Haley RL, Blackburn ML, Badger TM and Ronis MJ: Ethanol impairs estrogen receptor signaling resulting in accelerated activation of senescence pathways, whereas estradiol attenuates the effects of ethanol in osteoblasts. J Bone Miner Res. 24:221–230. 2009. View Article : Google Scholar
19	Kyung TW, Lee JE, Phan TV, Yu R and Choi HS: Osteoclastogenesis by bone marrow-derived macrophages is enhanced in obese mice. J Nutr. 139:502–506. 2009. View Article : Google Scholar : PubMed/NCBI
20	Premaor MO, Pilbrow L, Tonkin C, Parker RA and Compston J: Obesity and fractures in postmenopausal women. J Bone Miner Res. 25:292–297. 2010. View Article : Google Scholar : PubMed/NCBI
21	Felson DT, Zhang Y, Hannan MT and Anderson JJ: Effects of weight and body mass index on bone mineral density in men and women: the Framingham study. J Bone Miner Res. 8:567–573. 1993. View Article : Google Scholar : PubMed/NCBI
22	Akridge M, Hilgers KK, Silveira AM, Scarfe W, Scheetz JP and Kinane DF: Childhood obesity and skeletal maturation assessed with Fishman’s hand-wrist analysis. Am J Orthod Dentofacial Orthop. 132:185–190. 2007.PubMed/NCBI
23	Macri EV, Gonzales Chaves MM, Rodriguez PN, Mandalunis P, Zeni S, Lifshitz F and Friedman SM: High-fat diets affect energy and bone metabolism in growing rats. Eur J Nutr. 51:399–406. 2012. View Article : Google Scholar : PubMed/NCBI
24	Yajnik CS and Yudkin JS: The Y-Y paradox. Lancet. 363:1632004. View Article : Google Scholar : PubMed/NCBI
25	Bielohuby M, Matsuura M, Herbach N, Kienzle E, Slawik M, Hoeflich A and Bidlingmaier M: Short term exposure to low-carbohydrate, high-fat diets induces low bone mineral density and reduces bone formation in rats. J Bone Miner Res. 25:275–284. 2010. View Article : Google Scholar : PubMed/NCBI