Mechanisms of Disease: is osteoporosis the obesity of bone?

Rosen, Clifford J.; Bouxsein, Mary L.

doi:10.1038/ncprheum0070

Cited by 856 publications

(726 citation statements)

References 49 publications

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“…These findings fit with existing hypotheses that a reciprocal or inverse relationship exists between adipogenesis and osteogenesis in the marrow microenvironment. 24,25 However, these authors did not study the effects of insulin. According to our data, lactoferrin also downregulated 3T3-L1 differentiation, decreasing the formation of lipid droplets.…”

Section: Discussionmentioning

confidence: 99%

Lactoferrin increases 172ThrAMPK phosphorylation and insulin-induced p473SerAKT while impairing adipocyte differentiation

et al. 2009

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Objective: Lactoferrin is a pleiotropic glycoprotein of the innate immune system with known effects on immunomodulation and cell differentiation. To gain an insight into the interaction among obesity, inflammation and insulin action, we aimed to examine the effects of lactoferrin on adipogenesis and the response to insulin in human hepatocarcinoma (HepG2) and 3T3-L1 cell lines. Design: The cells were cultured with increasing lactoferrin concentration under non-inflammatory, inflammatory and standard conditions. The response to insulin was evaluated through 473Ser AKT phosphorylation. The effects of lactoferrin on adipogenesis were studied through the expression of different lipogenic markers, AMP-activated protein kinase (AMPK) activation, retinoblastoma (Rb) activity and Oil Red O staining in 3T3-L1 cells. Results: Lactoferrin increased dose-dependent insulin-induced 473Ser AKT phosphorylation in both cell lines. Inflammationinduced decreased 473Ser AKT phosphorylation was also rescued by lactoferrin. In addition, lactoferrin led to increased p172Thr AMPK during 3T3-L1 differentiation and to decreased adipogenesis (as shown by decreased expression of fatty acid synthase, acetyl-coenzyme A carboxylase-a and peroxisome proliferator-activated receptor-g in parallel with decreased formation of lipid droplets). Lactoferrin also increased dose-dependent Rb activity (expression and hypophosphorylation) during 3T3-L1 differentiation. Conclusion: Lactoferrin administration increased insulin-induced 473Ser AKT phosphorylation, even in those conditions wherein the response to insulin was downregulated, and led to blunted adipogenesis in the context of increased p172Thr AMPK and Rb activity.

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Section: Discussionmentioning

confidence: 99%

Lactoferrin increases 172ThrAMPK phosphorylation and insulin-induced p473SerAKT while impairing adipocyte differentiation

et al. 2009

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“…Rosen and Bouxsein asked a provocative question: does fat infiltration in the bone marrow cause low bone mass, or is it only a result of bone loss [114]? There is growing evidence that leptin as well as adiponectin can modulate bone metabolism [115,116,117].…”

Section: Resistin and Bone Metabolismmentioning

confidence: 99%

The role of resistin as a regulator of inflammation: Implications for various human pathologies

Filková

Haluzı́k

Šenolt

2009

Clinical Immunology

359

297

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“…(20) There are strong reasons to expect a pathophysiologic linkage between fat and bone tissue. Osteoblasts and adipocytes in bone marrow originate from the same mesenchymal stem cells, (21) normal aging is associated with a high incidence of both osteoporosis and bone marrow adiposity, (22,23) and both bone remodeling and adiposity are regulated by the hypothalamus and sympathetic nervous system. (22) Fat and bone are also linked biomechanically.…”

mentioning

confidence: 99%

Fat mass accumulation compromises bone adaptation to load in finnish women: A cross-sectional study spanning three generations

Xu¹,

Nicholson²,

Wang³

et al. 2010

Journal of Bone and Mineral Research

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Body weight and lean mass correlate with bone mass, but the relationship between fat mass and bone remains elusive. The study population consisted of 396 girls and 138 premenopausal mothers and 114 postmenopausal grandmothers of these girls. Body composition and tibial length were assessed using dual-energy X-ray absorptiometry (DXA), and bone traits were determined at the tibia using peripheral quantitative computed tomography (pQCT) in the girls at the ages of 11.2 AE 0.8, 13.2 AE 0.9, and 18.3 AE 1.0 years and in the mothers (44.7 AE 4.1 years) and grandmothers (70.7 AE 6.3 years). The values of relative bone strength index (RBSI), an index reflecting the ratio of bone strength to the load applied on the tibia, were correlated among family members (all p < .05). The mean values of RBSI were similar among 11-and 18-year-old girls and premenopausal women but significantly lower in 13-year-old girls and postmenopausal women. However, in each age group, subjects in the highest BMI tertiles had the lowest RBSI values (all p < .01). RBSI was inversely associated with body weight (all p < .01), indicating a deficit in bone strength relative to the applied load from greater body weight. RBSI was inversely associated with fat mass (all p < .001) across age groups and generations but remained relatively constant with increasing lean mass in girls and premenopausal women (all p > .05), indicating that the bone-strength deficit was attributable to increased fat mass, not lean mass. Moreover, the adverse effect of fat mass was age-dependent, with every unit increase in fat mass associated with a greater decrease in RBSI in pre-and postmenopausal women than in girls (all p < .001). This is largely due to the different capacity of young and adult bones to increase diaphyseal width by periosteal apposition in response to increased load. In summary, increasing body weight with fat accumulation is accompanied by an age-dependent relative bone-strength deficit in women because the beneficial effects of increased fat mass on bone, if any, do not compensate for the mechanical burden that it imposes. ß

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Mechanisms of Disease: is osteoporosis the obesity of bone?

Cited by 856 publications

References 49 publications

Lactoferrin increases 172ThrAMPK phosphorylation and insulin-induced p473SerAKT while impairing adipocyte differentiation

Lactoferrin increases 172ThrAMPK phosphorylation and insulin-induced p473SerAKT while impairing adipocyte differentiation

The role of resistin as a regulator of inflammation: Implications for various human pathologies

Fat mass accumulation compromises bone adaptation to load in finnish women: A cross-sectional study spanning three generations

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