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

Area of Science:

• Immunology
• Cellular Metabolism
• Nutritional Science

Background:

• Chronic inflammation is linked to metabolic diseases like obesity and type 2 diabetes.
• Increased glucose metabolism in immune cells may drive heightened immune responses.
• Previous studies suggest n-3 polyunsaturated fatty acids (PUFAs) impact cellular energy production.

Purpose of the Study:

• To investigate the direct effects of ALA and DHA on glucose metabolism in monocytes.
• To explore the molecular mechanisms underlying these metabolic changes.
• To assess the impact of ALA and DHA on inflammatory markers and reactive oxygen species.

Main Methods:

• THP-1 monocytes were treated with ALA or DHA (10-40 µmol/L) or control substances.
• Cellular bioenergetics were measured using Seahorse XFe24 and Oroboros O2k Oxygraph systems.
• Levels of IL-1β and reactive oxygen species were quantified.

Main Results:

• Both ALA and DHA significantly reduced oxidative phosphorylation in monocytes.
• Pyruvate dehydrogenase kinase 4 (PDK4) was identified as a potential mediator for DHA's effects.
• ALA and DHA decreased lipopolysaccharide-induced IL-1β production; DHA also increased reactive oxygen species.

Conclusions:

• ALA and DHA can modulate monocyte bioenergetics, potentially by upregulating PDK4.
• These n-3 PUFAs may influence immune cell function and inflammation through metabolic pathway re-wiring.
• The findings suggest a novel mechanism for how omega-3 fatty acids exert anti-inflammatory effects.