Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/6/2019
Publication Date: 9/11/2019
Citation: Cao, J.J., Gregoire, B.R., Michelsen, K.G., Picklo, M.J. 2019. Increasing dietary fish oil reduces adiposity and mitigates bone deterioration in growing C57BL/6 mice fed a high-fat diet. Journal of Nutrition. https://doi.org/10.1093/jn/nxz215.
Interpretive Summary: Obesity is a major public health problem worldwide and a risk factor for many chronic diseases. The type of fat influences the degree of obesity and obesity-related chronic diseases. It has been demonstrated that long-chain n-3 (LCn3) polyunsaturated fatty acids have positive effects on bone health. We investigated whether dietary LCn3 would improve bone-related outcomes in a high-fat (HF) induced obesity mouse model. We found that the HF diet decreased bone mass in while increasing bone resorption, adipose tissue proinflammatory cytokine expression, and total n-6 fatty acids in serum and bone. In contrast, increasing dietary LCn3 content in the form of fish oil improved bone mass in animals fed the HF diet and increased LCn3 in serum and bone while lowering bone resorption and proinflammatory cytokine expression in adipose tissue. Findings from this study demonstrate that fish oil rich in LCn3 decreases bone resorption and is beneficial in lowering obesity-induced detrimental bone effects.
Technical Abstract: Intake of total fat, particularly saturated fatty acids (SFA), is inversely associated with bone density in humans. Epidemiologic and animal studies show that long-chain n-3 (LCn3) polyunsaturated fatty acids (PUFA) are beneficial to skeletal health. This study tested the hypothesis that dietary LCn3 would decrease adiposity and improve bone-related outcomes by reducing bone turnover in growing mice fed a high-fat (HF) obesogenic diet. Male C57BL/6 mice at 6-wk-old were randomly assigned to 6 treatment groups in a 2x3 factorial design and fed either a normal-fat diet [NF, 3.85 kcal/g and 10% energy as fat] or a HF diet (4.73 kcal/g and 45% energy as fat) containing either 0, 3, or 9% energy as fish oil (FO) ad libitum for 6 mos. Results showed that compared to the NF, mice fed the HF had lower food but the same energy intake. The HF diet increased the expression of the adipose tissue proinflammatory cytokine, Tnfa, increased serum concentrations of leptin and tartrate-resistant acid phosphatase (TRAP), a bone resorption marker, and decreased serum concentrations of bone formation markers, osteocalcin and bone specific alkaline phosphatase. FO decreased fat mass, serum TRAP and adiponectin, and adipose tissue Tnfa expression but did not affect lean mass. In agreement with the elevation in dietary FO content, bone content of LCn3 and total n-3 fatty acids were increased. Conversely, FO intake decreased bone concentrations of the n-6 PUFA 18:2n-6, 20:4n-6, 22:4n-6, and total n-6. The HF diet decreased femoral bone mass, connectivity density (Conn.Dn), and trabecular number and had higher trabecular separation. Mice fed the HF with 3% energy FO had higher bone mass than those fed the HF without FO. These data indicate that dietary LCn3 decrease adiposity and increase total content of LCn3 in bone. Increasing FO intake can mitigate high-fat diet induced bone deterioration in growing mice possibly by reducing inflammation and bone resorption.