Fructose consumption does not worsen bone deficits resulting from high-fat feeding in young male rats

Abstract

Dietary-induced obesity (DIO) resulting from high-fat (HF) or high-sugar diets produces a host of deleterious metabolic consequences including adverse bone development. We compared the effects of feeding standard rodent chow (Control), a 30% moderately HF (starch-based/sugar-free) diet, or a combined 30%/40% HF/high-fructose (HF/F) diet for 12weeks on cancellous/cortical bone development in male Sprague-Dawley rats aged 8weeks. Both HF feeding regimens reduced the lean/fat mass ratio, elevated circulating leptin, and reduced serum total antioxidant capacity (tAOC) when compared with Controls. Distal femur cancellous bone mineral density (BMD) was 23-34% lower in both HF groups (p<0.001) and was characterized by lower cancellous bone volume (BV/TV, p<0.01), lower trabecular number (Tb.N, p<0.001), and increased trabecular separation versus Controls (p<0.001). Cancellous BMD, BV/TV, and Tb.N were negatively associated with leptin and positively associated with tAOC at the distal femur. Similar cancellous bone deficits were observed at the proximal tibia, along with increased bone marrow adipocyte density (p<0.05), which was negatively associated with BV/TV and Tb.N. HF/F animals also exhibited lower osteoblast surface and reduced circulating osteocalcin (p<0.05). Cortical thickness (p<0.01) and tissue mineral density (p<0.05) were higher in both HF-fed groups versus Controls, while whole bone biomechanical characteristics were not different among groups. These results demonstrate that "westernized" HF diets worsen cancellous, but not cortical, bone parameters in skeletally-immature male rats and that fructose incorporation into HF diets does not exacerbate bone loss. In addition, they suggest that leptin and/or oxidative stress may influence DIO-induced alterations in adolescent bone development.

Keywords: Adipose; Adiposity; Diet; Fat; Osteoporosis; Sugar.

Figure 1

Representative microcomputed tomography (μCT) images of cancellous bone at the distal femoral metaphysis region of interest (ROI) from animals fed standard rodent chow (Control), a 30% moderately high-fat (HF) diet, or a combined 30% high-fat/40% high-fructose (HF/F) diet. Animals receiving HF and HF/F diets exhibited reduced cancellous volumetric bone mineral density (vBMD, Lower Panel) and reduced trabecular spicules indicative of cancellous osteopenia (data presented in Table 2). Data are mean ± SEM from n = 7–10/group. ***p<0.001 vs. Control.

Figure 2

Histologic images of cancellous bone (stained black) and adipocytes (white) at the proximal tibia from animals fed standard rodent chow (Control), a 30% moderately high-fat (HF) diet, or a combined 30% high-fat/40% high-fructose (HF/F) diet. Animals receiving HF and HF/F diets exhibited increased adipocyte density (lower panel) and reduced cancellous bone volume (data presented in Table 4). Data are mean ± SEM from n = 7–10/group. *p<0.05 vs. Control

Figure 3

Figure 3A–B. Serum measurements of A) TRAP5b (circulating marker of bone resorption) and B) osteocalcin (circulating marker of bone formation) from animals fed standard rodent chow (Control), a 30% moderately high-fat (HF) diet, or a 30% combined high-fat/40% high-fructose (HF/F) diet. Data are mean ± SEM from n = 7–10/group. *p<0.05 vs. Control.

Figure 4

Figure 4A–B. Serum measurements of A) leptin concentrations and B) total antioxidant capacity (tAOC) from animals fed standard rodent chow (Control), a 30% moderately high-fat (HF) diet, or a combined 30% high-fat/40% high-fructose (HF/F) diet. Data are mean ± SEM from n = 8–10/group. *p<0.05 vs. Control.