Nutrients. , 2020., Nov 13;12(11):3494. doi: 10.3390/nu12113494.

The Role of Omega-3 Polyunsaturated Fatty Acids from Different Sources in Bone Development

Rozner, R Vernikov, J Griess-Fishheimer, S et al.


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.

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Key Points

Previous research shows a positive effect of n-3 PUFAs on bone development and quality in fat-1 transgenic mice (expressing the c-elegans n-3 desaturase). In the present study, diets rich in n-3 PUFAs were used to further elucidate the role of different sources of n-3 PUFAs in bone development. In addition, to examine the molecular mechanism of bone formation induced by n-3 PUFAs, RNA-seq analysis of whole bones was performed.

This study describes the role of different dietary sources of n-3 PUFAs in skeletal development and bone quality. Findings included that dietary n-3 PUFAs: 1) contributed to improved mechanic and morphometric properties of the bone, hence to improved bone quality; 2) decrease Hepatic and Serum Fat Levels;3) high amount of ALA in the flaxseed oil diet reduced production of the n-6 LC-PUFAs; 4) affect bone quality by influencing different osseous tissues; while flaxseed oil improved trabecular bone properties, fish oil enhanced mineralization. The findings show a link between the consumption of n-3 PUFAs and bone circadian rhythm and improved bone phenotype. Together with evidence from the bone-specific KO of clock genes, a pivotal role of dietary n-3 PUFAs may be in regulating bone quality is mediated by the peripheral circadian clock system. The results emphasize the importance of integrating various sources of n-3 PUFAs into the diet from an early age. Omega-3 may be an important nutrient to include in diets that promote bone health especially in view of the general population’s tendency over the past three decades toward excessive consumption of n-6 PUFAs.