Omega-3 polyunsaturated fatty acids modify glucose metabolism in THP-1 monocytes

Chronic inflammation is a driving factor in diseases like obesity and type 2 diabetes. Enhanced cellular glucose metabolism may contribute to heightened immune activation. A human supplementation trial showed that the n-3 PUFA α-linolenic acid (ALA) reduced oxidative phosphorylation in monocytes. Our objective here is to assess the direct effects of ALA and docosahexaenoic acid (DHA) on glucose metabolism in a cell culture model and to explore possible molecular mechanisms. THP-1 monocytes were treated with 10-40 µmol/L of ALA or DHA and compared with vehicle and oleic acid controls. The Seahorse XFe24 and Oroboros O₂k Oxygraph systems were used to approximate catabolic rates in the presence of glucose. Both ALA and DHA reduced oxidative phosphorylation. We identified pyruvate dehydrogenase kinase 4 (PDK4) as a possible mechanistic candidate explaining the effect of DHA. Additionally, both n-3 PUFAs reduced lipopolysaccharides-induced IL-1β production, while only DHA increased reactive oxygen species to a small but significant extent. Our data suggest that ALA and DHA trigger a re-wiring of bioenergetic pathways in monocytes, possibly via the upregulation of PDK4. Given the close relationship between cell metabolism and immune cell activation, this may represent a novel mechanism by which n-3 fatty acids modulate immune function and inflammation.