Abstract
BACKGROUND: Linoleic acid (LA; 18:2n-6) has been considered to promote low-grade chronic inflammation and adiposity. Studies show adiposity and inflammation are inversely associated with bone mass. OBJECTIVES: This study tested the hypothesis that decreasing the dietary ratio of LA to α-linolenic acid (ALA, 18:3n-3), while keeping ALA constant, mitigates high-fat diet (HF)-induced adiposity and bone loss. METHODS: Male C57BL/6 mice at 6 wk old were assigned to 4 treatment groups and fed 1 of the following diets ad libitum for 6 mo: a normal-fat diet (NF; 3.85 kcal/g and 10% energy as fat) with the ratio of the PUFAs LA to ALA at 6; or HFs (4.73 kcal/g and 45% energy as fat) with the ratio of LA to ALA at 10:1, 7:1, or 4:1, respectively. ALA content in the diets was kept the same for all groups at 1% energy. Bone structure, body composition, bone-related cytokines in serum, and gene expression in bone were measured. Data were analyzed using 1-factor ANOVA. RESULTS: Compared with those fed the NF, mice fed the HFs had 19.6% higher fat mass (P < 0.01) and 13.5% higher concentration of serum tartrate-resistant acid phosphatase (TRAP) (P < 0.05), a bone resorption cytokine. Mice fed the HFs had 19.5% and 12.2% lower tibial and second lumbar vertebral bone mass, respectively (P < 0.01). Decreasing the dietary ratio of LA to ALA from 10 to 4 did not affect body mass, fat mass, serum TRAP and TNF-α, or any bone structural parameters. CONCLUSIONS: These data indicate that decreasing the dietary ratio of LA to ALA from 10 to 4 by simply reducing LA intake does not prevent adiposity or improve bone structure in obese mice.
Link to Full Text
Key Points
Contradictory evidence exists as to whether excessive intake of n–6 PUFAs (mainly LA) and a high ratio of n–6 to n–3 PUFAs are linked to the pathogenesis of cardiovascular diseases or skeletal health. The inconsistent findings could be due to many studies that not only modified the amount of LA but also modified the amount of ALA and/or EPA + DHA to achieve the desired ratio.
Whether the ratio of n–6 to n–3 PUFAs in the form of LA:ALA affects bone health in diet-induced obesity has not been investigated. In this study, the impact of varying ratios of LA to ALA from 10 to 4 on bone health in an obese mouse model by changing the amount of LA in the diets was studied. Because the total quantity of n–6 and n–3 PUFAs or the type of n–3 PUFAs may likely affect bone health, ALA amounts remained constant at 1% energy for all obesogenic diets in this study. A diet-induced obesity mouse model with animals being fed diets with 45% energy as fat but varying ratios of LA to ALA for 6 mo.
The major findings of this study were that after consuming the respective diet for 6 mo, 1) LA content in serum and bone decreased whereas ARA content in serum and bone did not change in mice as the ratio of LA to ALA decreased from 10:1 to 4:1; 2) ALA concentrations in serum and bone were unaltered, as expected by design; and 3) the changes in ratios of LA to ALA in diets, and ratios of n–6 to n–3 PUFAs in serum and bone were not accompanied by any changes in fat mass, proinflammatory and bone resorption cytokines in serum, or bone structural parameters in tibia or lumbar vertebrae. Although the effects of n–6 and n–3 PUFAs on bone would likely be found in animals with elevated inflammatory status such as in aging and estrogen deficiency, obesity is also associated with a state of elevated chronic low-grade inflammation and bone deterioration.
In summary, the data demonstrates that HF-induced obesity is detrimental to bone microstructure in mice and decreasing intake of LA while maintaining constant ALA does not alter serum and bone content of ARA, adiposity, or bone structure in obese mice. These findings suggest that the type and the amount of n–3 PUFAs rather than the amount of n–6 PUFAs or the ratio of LA to ALA should be considered as a preferred dietary strategy to reduce adiposity and improve bone health.