Diet and gene interactions influence the skeletal response to polyunsaturated fatty acids

Diets rich in omega-3s have been thought to prevent both obesity and osteoporosis. However, conflicting findings are reported, probably as a result of gene by nutritional interactions. Peroxisome proliferator-activated receptor-gamma (PPAR gamma) is a nuclear receptor that improves insulin sensitivity but causes weight gain and bone loss. Fish oil is a natural agonist for PPAR gamma and thus may exert its actions through the PPAR gamma pathway. We examined the role of PPAR gamma in body composition changes induced by a fish or safflower oil diet using two strains of C57BL/6J (B6); i.e. B6.C3H-6T (61) congenic mice created by backcrossing a small locus on Chr 6 from OH carrying 'gain of function' polymorphisms in the PpAR gamma gene onto a B6 background, and C57BL/6J mice. After 9 months of feeding both diets to female mice, body weight, percent fat and leptin levels were less in mice fed the fish oil vs those fed safflower oil, independent of genotype. At the skeletal level, fish oil preserved vertebral bone mineral density (BMD) and microstructure in B6 but not in 6T mice. Moreover, fish oil consumption was associated with an increase in bone marrow adiposity and a decrease in BMD, cortical thickness, ultimate force and plastic energy in femur of the 61 but not the B6 mice. These effects paralleled an increase in adipogenic inflammatory and resorption markers in 61 but not B6. Thus, compared to safflower oil, fish oil (high ratio omega-3/-6) prevents weight gain, bone loss, and changes in trabecular microarchitecture in the spine with age. These beneficial effects are absent in mice with polymorphisms in the PpAR gamma gene (6T), supporting the tenet that the actions of n-3 fatty acids on bone microstructure are likely to be genotype dependent. Thus caution must be used in interpreting dietary intervention trials with skeletal endpoints in mice and in humans. (C) 2014 Elsevier Inc. All rights reserved.