High-fat, sucrose diet impairs geometrical and mechanical properties of cortical bone in mice

Abstract

Exposure to diets high in fat and sucrose can induce hyperinsulinaemia, affect Ca and Mg metabolism, and alter bone mineralisation and mechanical properties. The present study assessed morphological and mechanical changes in a murine model exposed to a high-fat/sucrose (HFS) diet, as well as corresponding molecular and endocrine markers of bone turnover. Female C57BL/6 mice (aged 9 weeks) consumed either a low-fat, complex carbohydrate diet or an HFS diet for 10 weeks. At the end of the 10 weeks, serum was collected for biochemical analysis. Tibiae from half the mice (n 15) were randomly selected to be micro-computed tomography scanned and tested to failure in cantilever bending, while the remaining half were prepared for real-time PCR analysis. Serum tartrate-resistant acid phosphatase was significantly elevated in HFS mice, while osteocalcin remained unchanged. Both body mass and percentage body fat were greater in mice fed HFS diet. After adjusting for body mass, tibial structural and morphological properties were adversely affected in the HFS cohort. Cortical thickness, cross-sectional area, and load at maximum were all significantly lower in mice fed HFS diet. Receptor activator of nuclear factor kb ligand (RANKL) mRNA was significantly upregulated in HFS mice, but osteoprotegerin/RANKL mRNA ratio remained unchanged between cohorts. Moreover, cyclo-oxygenase-2 mRNA tended to be increased in HFS. Thus, ingestion of an HFS diet had a significant adverse effect on mouse bone morphology and mechanics, and these effects were likely due to elevated osteoclast activity associated with the inflammatory state of obesity, and not necessarily osteoclast recruitment/ proliferation.Cortical bone: High-fat/sucrose diet: Biomechanics: C57BL/6 mice The changing face of disease aetiology over the past century has brought to the forefront the need to examine the environmental or modifiable risk factors that have influenced the epidemic of chronic disease afflicting a majority of the Western world. Nutritional status is a readily modifiable risk factor linked to numerous chronic conditions, including CHD, cancer, obesity, diabetes and osteoporosis (1,2) . Nonetheless, despite the prevalence of research linking poor dietary choices to chronic disease status, the nutritional patterns presently dominating most Western nations continue to be high in saturated fats, Na and refined carbohydrates from sugars, cereals and dairy products, and low in fruits, vegetables and lean protein (3) .Considerable effort has focused on discovering the underlying nutritional factors that predispose an individual to osteopenia or osteoporosis and subsequent fracture (4) . Much research has concentrated on the role of Ca and vitamin D metabolites influencing bone morphology and mechanics; however, macronutrients such as fat, protein and carbohydrate also play a vital role in bone health (5) . Considered independently, consumption of diets composed of large amounts of saturated fat has been documented to cause the formation of insoluble soap complexe...

Obesity-related changes in bone structural and material properties in hyperphagic OLETF rats and protection by voluntary wheel running

“…Both cortical and trabecular bones appear to be affected by diet-induced obesity in rapidly growing rodents. Long-term diet-induced obesity reduces the thickness and cross-sectional area of the cortical shell of the femoral neck [40] and tibia [41], significantly reducing the structural properties (loads, energies, stiffness normalized to body weight) [40]. Data from studies of diet-induced obesity suggest that the reductions in structural properties appear due, in part, to changes in trabecular microarchitecture (i.e., increased porosity [42], decreased trabecular number, increased trabecular separation and reduced connectivity [39,43,44] and a shift in trabecular organization from plate-to rod-like, which is reduced in strength [39,45].…”

“…Bone resorption appears to be increased with dietinduced obesity as evidenced by increased serum concentrations of the resorption markers TRAP5b [41,43] and CTX [4,39] and by increased RANKL [41]. In addition, osteoclastogenesis and osteoclast activity in vitro are increased in bone cells from obese animals compared with lean controls [39,41,43,44]. In addition, compared with controls, diabetic rats have reduced osteoblast function and rates of bone formation [46,47].…”

Bezafibrate enhances proliferation and differentiation of osteoblastic MC3T3-E1 cells via AMPK and eNOS activation

“…To examine the mineralization of the MC3T3-E1 cells, the cells were seeded at 5×10 4 per well in 24-well plates with differentiation medium containing vehicle (DMSO) or bezafibrate (100 μmol/L). After 21 d, the formation of mineralizing plaques was visualized by Alizarin red staining.…”

“…Hypercholesterolemia was reported to be associated with lower bone mineral density (BMD) [2,3] . An animal model study has also demonstrated some detrimental effects of dyslipidemia on bone metabolism [4] . Fibrate use, including bezafibrate, was associated with a reduced odds of vertebral fractures in men and women [5] .…”

Fructose Consumption Does Not Worsen Bone Deficits Resulting From High-Fat Feeding in Young Male Rats

“…[5,8,10] In contrast, a combined high-fat/sucrose diet impairs lumbar and femoral neck strength in rodents, likely a result of smaller bone cross-sectional area and/or reduced cortical bone area in comparison to a low-fat/complex carbohydrate diet. [37,51] Interestingly, we observed that the cortical bone compartments at the distal femur and femoral diaphysis of HF and HF/F animals exhibited increased Ct.Th and Ct.Ar/Tt.Ar and densitometric characteristics, although, these changes did not improve whole bone mechanical characteristics in comparison with Controls. Regardless, our findings indicate that HF feeding produced divergent effects in the cortical and cancellous bone compartments, a concept that has been proposed by others.…”