Abstract

N-3 polyunsaturated fatty acids (PUFAs) are essential nutrients that must be obtained from the diet. We have previously showed that endogenous n-3 PUFAs contribute to skeletal development and bone quality in fat-1 mice. Unlike other mammals, these transgenic mice, carry the n-3 desaturase gene and thus can convert n-6 to n-3 PUFAs endogenously. Since this model does not mimic dietary exposure to n-3 PUFAs, diets rich in fish and flaxseed oils were used to further elucidate the role of n-3 PUFAs in bone development. Our investigation reveals that dietary n-3 PUFAs decrease fat accumulation in the liver, lower serum fat levels, and alter fatty acid (FA) content in liver and serum. Bone analyses show that n-3 PUFAs improve mechanical properties, which were measured using a three-point bending test, but exert complex effects on bone structure that vary according to its source. In a micro-CT analysis, we found that the flaxseed oil diet improves trabecular bone micro-architecture, whereas the fish oil diet promotes higher bone mineral density (BMD) with no effect on trabecular bone. The transcriptome characterization of bone by RNA-seq identified regulatory mechanisms of n-3 PUFAs via modulation of the cell cycle and peripheral circadian rhythm genes. These results extend our knowledge and provide insights into the molecular mechanisms of bone remodeling regulation induced by different sources of dietary n-3 PUFAs.

Highlights

  • The skeleton is a unique system that performs mechanical, storing, metabolic, and protective functions

  • To study the effect of dietary n-3 polyunsaturated fatty acids (PUFAs) from different sources on skeletal development, 3-week-old female C57BL6 mice were divided into three groups and fed isocaloric diets that differed only in their source of fat (Table 1) for 3 or 6 weeks

  • The control diet was rich in n-6 PUFAs, while both flaxseed oil and fish oil diets were rich in n-3 PUFAs (Table 2)

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Summary

Introduction

The skeleton is a unique system that performs mechanical, storing, metabolic, and protective functions. Bone is a highly dynamic organ undergoing constant remodeling in order to maintain optimum mechanical functions. Bone tissue is continuously degraded by bone resorbing cells—the osteoclasts—which are replaced by new bone-forming cells called osteoblasts [1]. The development and differentiation of these two distinct cells are tightly regulated by numerous endogenous substances, including growth factors, hormones, cytokines, and neurotransmitters. Genetics contribute considerably to peak bone mass (PBM), an individual’s full genetic potential can be achieved through proper nutrition and exercise [2].

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