INFORM October 2025

10 • inform October 2025, Vol. 36 (9)

ically, and that really improves overall metabolic health and joint health.” Philip Calder, professor of nutritional immunology at the University of Southampton, United Kingdom, said in an email that the study’s findings are consistent with previous research on the connections between dietary fatty acids and inflamma tion-related diseases. In 2015, Thiago Belchoir published research demonstrat ing that omega-3 fatty acids protect against diet-induced obesity and inflammation through the transcription fac tor PPARγ (https://doi.org/10.1002/mnfr.201400914). And in 2020, Guilak and colleagues showed that fat-1 transgenic mice exhibited reduced OA severity (https://doi.org/10.1186/ s13075-020-02170-7). FATTY ACIDS AND CELLULAR AGING Guilak’s current study also indicates that obesity causes pre mature joint aging. The research shows that high-fat diet-in duced obesity increases cellular senescence, a cellular state associated with aging where cells are alive but no longer divid ing. Higher amounts of senescence markers—β-galactosidase, p21, and p16—were measured in the fat tissues and joints of obese mice with DMM-induced OA. These findings suggest that high-fat diets may lead to premature cellular aging and Some omega-6 fatty acids are common elements of the human diet. Linoleic acid (LA), found in grapeseed, cotton seed, sunflower, corn, and canola oils, as well as nuts, seeds, mixed grains, and meats, is the most prevalent omega-6 fatty acid in the diet. When metabolized, LA breaks down into other fatty acids, including arachidonic acid (ARA). ARA is also found in meat, eggs, and other foods and is a critical component of cell membranes. It also contributes to brain development, and wound healing (https://doi.org/10.1016/j.jare.2017.11.004). If there is too little LA in the diet, the body’s skin and epi thelial barriers can become compromised. There is also evi dence that higher consumption of LA improves heart and metabolic health. Research has shown that higher levels of LA in the blood are tied to lower risks of coronary heart disease, stroke, and type 2 diabetes. It remains unclear how LA is medi ating these effects. In a 2024 review paper, Kristina H. Jackson and colleagues wrote: “Taken together, these epidemiological findings strongly suggest that higher LA (and in some settings, ARA) levels are linked with improved outcomes” (https://doi. org/10.1186/s12944-024-02246-2). The fatty acid controversy Both omega-6 and omega-3 fatty acids are essential to health. Despite the excess of omega-6 in the typical Western diet and their association with obesity and systemic inflammation, no single element of the human diet, is a villain. Furthermore, not all omega-6 fatty acids behave the same way inside the body.

degeneration and synovitis, inflammation of the synovial mem brane that lines the joint. The researchers analyzed the ther apeutic effects on the trabeculae, spongy bone structures in joints that distribute load and absorb shock. Mice with DMM induced OA had fewer but thicker trabeculae with greater sep aration. Fat-1 gene therapy counteracted these effects in bone microarchitecture. CONSISTENT OUTCOMES Through this series of experiments, Guilak and his colleagues were able to use gene therapy to alter the systemic fatty acid composition and inflammatory profile in obese mice, which reduced the severity of OA. “They found that injecting into the whole mouse this virus that contains this gene ... did result in improvements in OA outcomes,” said Jefferies. “The histology was better, and it does appear, probably, that the inflammation around the joint was better. And also, interestingly enough, it looks like the mice weighed less even when they were fed a high-fat diet.” Guilak emphasized that the study indicates fat-1 con verts omega-6 fatty acids into even more beneficial ome ga-3s, thereby improving metabolism and joint health. He said through the expression of fat-1 , you can “take your hamburger and fries and convert it to a salmon oil in your body automat