Males born growth restricted have bone deficits and increased predisposition to obesity and cardiometabolic disease. Obesity is a state of chronic inflammation associated with increased levels of leptin. Leptin has central and peripheral effects which may negatively or positively regulate bone metabolism. We aimed to determine whether consuming a high fat diet (HFD) would exacerbate pre-existing bone deficits in males born small.
Uteroplacental insufficiency was induced by bilateral uterine vessel ligation (Restricted) or sham (Control) surgery on embryonic day 18 in female Wistar-Kyoto rats. Male offspring consumed either standard chow or HFD (23% fat) from 5 weeks to 6 months of age. At post mortem (6 months) fat pads were weighed, plasma leptin concentrations measured and right femora were quantified by pQCT analysis.
Restricted males were lighter at birth compared to Controls (p<0.05). At 6 months, Control and Restricted males consuming HFD were heavier compared to Chow which was associated with increased dorsal fat mass and circulating leptin (p<0.05), irrespective of birth weight. Trabecular content and density were increased in males consuming HFD (p<0.05), irrespective of birth weight. Cortical content was reduced in Restricted males only (p<0.05) irrespective of diet while cortical density remained unaffected. Bone geometry measures of cortical thickness, periosteal circumference and endosteal circumference were not different. Bending strength was reduced in Restricted males compared to Controls (p<0.05), irrespective of diet.
This study highlights that a HFD did not further exacerbate pre-existing bone deficits in males born small. Increased circulating leptin may be responsible for increasing trabecular bone. Decreased bending strength indicates that males born small have increased risk of fracture. Additional postnatal hits such as aging and remaining sedentary may exacerbate bone deficits. Exercise interventions may reduce excess fat mass, leptin levels and bone deficits that are associated with growth restriction and decrease fracture risk.