Enhancement of the synthesis of n-3 PUFAs in fat-1 transgenic mice inhibits mTORC1 signalling and delays surgically induced osteoarthritis in comparison with wild-type mice

Huang MJ, Wang L, Jin DD, Zhang ZM, Chen TY, Jia CH, Wang Y, Zhen XC, Huang B, Yan B, Chen YH, Li SF, Yang JC, Dai YF, Bai XC · Annals of the Rheumatic Diseases

The cleanest available separation of omega-3 status from omega-3 dosing: no supplement was given, the animals simply had a different tissue fatty-acid composition. Cartilage destruction and osteophytosis were significantly reduced (p < 0.01), MMP-13 and ADAMTS-5 protein in articular cartilage were lower (p < 0.01), and chondrocyte loss and matrix loss were reduced. Both endogenous and exogenous n-3 downregulated mTORC1 and promoted chondrocyte autophagy.

Population

fat-1 transgenic mice, which make their own n-3 PUFAs from n-6, versus wild-type, after medial meniscus resection

Intervention

Genetically raised endogenous n-3 and lowered n-6 PUFA content

Comparator

Wild-type littermates in the same surgical model

Limitations

A transgenic mouse has a lifelong altered fatty-acid composition, which no diet reproduces. It tests the n-6:n-3 ratio hypothesis, not a supplement or a meal.