Bone Mass in Obese Diabetic Zucker Rats: Influence of Treadmill Running

Mathey, Jacinthe; Horcajada-Molteni, M.N.; Chanteranne, Brigitte; Picherit, Christel; Puel, Caroline; Lebecque, Patrice; Cubizoles, C.; Davicco, Marie-Jeanne; Coxam, Véronique; Barlet, J.P.

doi:10.1007/s00223-001-2077-8

Cited by 71 publications

(57 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This is consistent with the reduced bone size of leptin-deficient mice (Steppan et al 2000) and leptin-resistant rats (Mathey et al 2002), and with evidence of a relationship between bone size and circulating leptin concentrations in adolescent women (Matkovic et al 1997). It is also consistent with the recent report of Maor et al (2002) that leptin directly promotes chondrocyte growth.…”

Section: Discussionsupporting

confidence: 90%

Leptin directly regulates bone cell function in vitro and reduces bone fragility in vivo

Cornish

Callon²,

Bava³

et al. 2002

Journal of Endocrinology

400

294

View full text Add to dashboard Cite

Fat mass is an important determinant of bone density, but the mechanism of this relationship is uncertain. Leptin, as a circulating peptide of adipocyte origin, is a potential contributor to this relationship. Recently it was shown that intracerebroventricular administration of leptin is associated with bone loss, suggesting that obesity should be associated with low bone mass, the opposite of what is actually found. Since leptin originates in the periphery, an examination of its direct effects on bone is necessary to address this major discrepancy.Leptin (>10 11 M) increased proliferation of isolated fetal rat osteoblasts comparably with IGF-I, and these cells expressed the signalling form of the leptin receptor. In mouse bone marrow cultures, leptin (d10 11 M) inhibited osteoclastogenesis, but it had no effect on bone resorption in two assays of mature osteoclasts. Systemic administration of leptin to adult male mice (20 injections of 43 µg/day over 4 weeks) reduced bone fragility (increased work to fracture by 27% and displacement to fracture by 21%, P<0·001). Changes in tibial histomorphometry were not statistically significant apart from an increase in growth plate thickness in animals receiving leptin. Leptin stimulated proliferation of isolated chondrocytes, and these cells also expressed the signalling form of the leptin receptor.It is concluded that the direct bone effects of leptin tend to reduce bone fragility and could contribute to the high bone mass and low fracture rates of obesity. When administered systemically, the direct actions of leptin outweigh its centrally mediated effects on bone, the latter possibly being mediated by leptin's regulation of insulin sensitivity.

show abstract

Section: Discussionsupporting

confidence: 90%

Leptin directly regulates bone cell function in vitro and reduces bone fragility in vivo

Cornish

Callon²,

Bava³

et al. 2002

Journal of Endocrinology

400

294

View full text Add to dashboard Cite

show abstract

“…[8][9][10][11] While most of these studies were performed in mice, the osteopenia evident after intracerebroventricular (ICV)-application of leptin in sheep has helped to underscore the importance of leptin in the regulation of bone remodeling beyond rodents and established a large animal model of osteoporosis. [12][13][14][15][16][17] The female sheep is a suitable model of the investigation of osteoporosis therapies, because the ewe is a large remodeling animal. 18,19 Therefore the bone loss in ewe after long-term ICV-application of leptin is important beyond mechanistic insights, as it allows preclinical testing of drugs and osteosynthesis in a large non-rodent animal, as stipulated, for example, by the United States FDA.…”

mentioning

confidence: 99%

Low turnover osteoporosis in sheep induced by hypothalamic‐pituitary disconnection

Beil

Oheim

Barvencik

et al. 2012

Journal Orthopaedic Research

View full text Add to dashboard Cite

The hypothalamus is of critical importance in regulating bone remodeling. This is underscored by the fact that intracerebroventricular-application of leptin in ewe leads to osteopenia. As a large animal model of osteoporosis, this approach has some limitations, such as high technical expenditure and running costs. Therefore we asked if a surgical ablation of the leptin signaling axis would have the same effects and would thereby be a more useful model. We analyzed the bone phenotype of ewe after surgical hypothalamopituitary disconnection (HPD þ OVX) as compared to control ewe (OVX) after 3 and 12 months. Analyses included histomorphometric characterization, micro-CT and measurement of bone turnover parameters. Already 3 months after HPD we found osteopenic ewe with a significantly decreased bone formation (69%) and osteoclast activity (49%). After a period of 12 months the HPD group additionally developed an (preclinical) osteoporosis with significant reduction (33%) of femoral cortical thickness, as compared to controls (OVX). Taken together, HPD leads after 12 month to osteoporosis with a reduction in both trabecular and cortical bone caused by a low bone turnover situation, with reduced osteoblast and osteoclast activity, as compared to controls (OVX). The HPD-sheep is a suitable large animal model of osteoporosis. Furthermore our results indicate that an intact hypothalamo-pituitary axis is required for activation of bone turnover. ß

show abstract

“…For instance, the femora of fa/fa rats weigh less than those of their lean counterparts, and serum assays indicate that fa/fa rats have elevated parathyroid hormone levels and are hypercalciuric [26]. Consistent with these findings, other authors have found that Zucker rats show decreased total body BMD and BMC [28], decreased trabecular bone volume in the tibia and increased osteoclast surface [29], increased bone fragility and decreased bone strength [30], and lower percent ash content in the skeleton compared to lean rats [31].…”

Section: Bone Phenotype In Genetically Obese Mice and Ratsmentioning

confidence: 66%

Body Fat as a Regulator of Bone Mass: Experimental Evidence from Animal Models

Hamrick

Della‐Fera²,

Baile³

et al. 2009

Clinic Rev Bone Miner Metab

View full text Add to dashboard Cite

Animal models have proven valuable for elucidating the effects of body fat on bone metabolism, and this review highlights recent findings relevant for better understanding the relationship between adiposity and bone mass. Genetically obese mice and rats with altered leptin signaling consistently show reduced bone mass, demonstrating that leptin deficiency can contribute directly to osteopenia; however, the effect of leptin on bone is concentration dependent, such that relatively low doses of leptin stimulate bone formation, whereas high concentrations of leptin suppress bone formation and increase bone resorption. The hyperleptinemia associated with obesity and leptin receptor downregulation is therefore likely to have a negative impact on bone modeling and adaptation. Likewise, diets high in fat and sugar have been observed to increase bone fragility and decrease the accumulation of bone mineral in growing rodents. In vitro studies reveal that increasing concentrations of glucose and lipid can inhibit osteogenic differentiation of mesenchymal stem cells (MSCs), and instead direct these precursors toward the adipocyte lineage. Taken together, the evidence from animal studies indicates that excess body fat and obesogenic diets may attenuate the accretion of skeletal mass in growing animals, suggesting that low bone mass (relative to body weight) may be a potential side-effect of pediatric obesity.

show abstract

Bone Mass in Obese Diabetic Zucker Rats: Influence of Treadmill Running

Cited by 71 publications

References 0 publications

Leptin directly regulates bone cell function in vitro and reduces bone fragility in vivo

Leptin directly regulates bone cell function in vitro and reduces bone fragility in vivo

Low turnover osteoporosis in sheep induced by hypothalamic‐pituitary disconnection

Body Fat as a Regulator of Bone Mass: Experimental Evidence from Animal Models

Contact Info

Product

Resources

About