Decreasing the dietary ratio of n-6:n-3 polyunsaturated fatty acids by reducing intake of linoleic acid does not prevent adiposity or bone deterioration in obese mice

Authors: Cao, Jay; Gregoire, Brian; Michelsen, Kim; Picklo, Matthew

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/5/2020
Publication Date: 3/5/2020
Citation: Cao, J.J., Gregoire, B.R., Michelsen, K.G., Picklo, M.J. 2020. Decreasing the dietary ratio of n-6:n-3 polyunsaturated fatty acids by reducing intake of linoleic acid does not prevent adiposity or bone deterioration in obese mice. Journal of Nutrition. https://doi.org/10.1093/jn/nxaa044.
DOI: https://doi.org/10.1093/jn/nxaa044

Interpretive Summary: Obesity is associated with chronic low-grade inflammation and is detrimental to bone. Dietary modification of fatty acids can decrease inflammation, reduce adiposity, and improve health. American diets are high in n-6 polyunsaturated fatty acids (PUFA), mostly linoleic acid (LA, 18:2n-6), and lacking in n-3 PUFA, mainly alpha-linolenic acid (ALA, 18:3n-3). It was thought that intake of n-6 PUFA promotes low grade chronic inflammation and adiposity. In this study, we investigated whether decreasing the ratio of n-6:n-3 PUFA by reducing LA intake only affects adiposity or adiposity-induced bone changes in an obese mouse model. Our data demonstrate that a high-fat diet induced obesity is detrimental to bone microstructure and decreasing LA intake does not change adiposity or bone structure in obese mice. The findings from this study suggest that the amount of n-6 PUFA or the ratio of n-6:n3 PUFA may not be a dietary strategy used to reduce adiposity and improve bone health.

Technical Abstract: Linoleic acid (LA, 18:2n-6), a precursor for arachidonic acid which is the substrate for certain proinflammatory eicosanoids, has been considered to promote low grade chronic inflammation and adiposity, whereas n-3 fatty acids are considered to have anti-inflammatory properties and decrease adiposity. Studies show adiposity and inflammation are inversely associated bone mass. To investigate whether the ratio of n-6:n-3 polyunsaturated fatty acids (PUFA) mainly as linoleic acid and alpha-linolenic acid (ALA, 18:3n-3), when ALA was kept constant, affects adiposity or adiposity-induced changes in bone structure in mice fed a high-fat (HF) diet. Therefore, we hypothesized that decreasing dietary LA content (i.e. n-6:n-3 PUFA ratio) mitigates high-fat diet (HF) induced adiposity and bone loss. Male C57BL/6 mice at 6-wk-old were randomly assigned to 4 treatment groups and fed one of the following diets ad libitum for 6 mo: a normal-fat diet (NF, 3.85 kcal/g and 10% energy as fat) or HF diets (4.73 kcal/g and 45% energy as fat) with n-6 PUFA at either 10, 7, or 4% energy, respectively. ALA content in the diets was kept the same for all groups at 1% energy, which is above the minimum requirement (0.68% energy) for rodents. Diets were formulated with a combination of high oleic sunflower oil, palm oil, safflower oil and flaxseed oil to achieve desired levels of fatty acids. Bone structural changes and body composition were measured. Compared to the NF, the HF increased body mass, fat mass, lean mass, serum concentrations of TNF-a and tartrate-resistant acid phosphatase (TRAP), a bone resorption cytokine. Mice fed the HF diets had lower tibial and 2nd lumbar vertebrae (L2) bone mass, tibial trabecular number and tibial connectivity density and higher tibial trabecular separation and L2 structural model index. Decreasing dietary n-6:n-3 PUFA ratio decreased the ratio of n-6:n-3 PUFA in serum and bone. The ratio of n-6:n-3 PUFA did not significantly affect body mass, fat mass, serum TRAP and TNF-a, or any trabecular and cortical bone structural parameters. These data indicate that decreasing the dietary n-6:n-3 PUFA ratio by reducing LA intake does not prevent adiposity or improve bone structure in obese mice. These findings suggest that modifying the amount and the type of n-3 could be more effective than simply reducing linoleic acid intake in mitigating adiposity and bone deterioration in obesity.