review · Nutrients
Omega-3 polyunsaturated fatty acids resolve inflammation by generating anti-inflammatory eicosanoids and specialised pro-resolving mediators, including resolvins, protectins, and maresins. Binding to the GPR120/FFAR4 receptor remodels phospholipid membranes, disrupts inflammatory signalling molecules, inhibits NF-κB and inflammasome activation, and lowers oxidative stress. These actions alleviate obesity and related metabolic disorders. Within adipose tissue, omega-3 fatty acids counteract hypoxia, curb immune cell infiltration and inflammation, improve insulin sensitivity, and decrease fat mass. They also address metabolic-associated steatotic liver disease, gut dysbiosis, and renal dysfunction, while serving as secondary prevention for individuals at risk of coronary heart disease. Furthermore, these fatty acids target specific pathophysiological mechanisms in chronic inflammatory conditions associated with obesity, such as inflammatory bowel disease, psoriasis, rheumatoid arthritis, osteoarthritis, and multiple sclerosis.
Obesity drives persistent inflammation that contributes to severe metabolic disorders and chronic diseases. Understanding how omega-3 fatty acids target cellular receptors and suppress inflammatory signals clarifies their biological value. This knowledge helps healthcare providers and patients assess how dietary or therapeutic fats can manage obesity-related complications, ranging from liver and kidney dysfunctions to inflammatory joint and bowel diseases.
Potential applications focus on clinical nutrition, therapeutics, and secondary prevention for cardiovascular conditions, metabolic liver disease, and chronic inflammatory disorders. The primary users are clinicians, dietitians, and nutraceutical or pharmaceutical developers. Because human clinical trials have already tested these fatty acids across various indications, therapies are near-market or already applied in clinical settings, though adoption depends on navigating specific clinical trial limitations.
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Omega-3 polyunsaturated fatty acids (n-3 PUFAs) are known to help resolve inflammation through generation of anti-inflammatory eicosanoids and specialized pro-resolving mediators, including resolvins, protectins, and maresins. Through binding to the GPR120/FFAR4 receptor, their beneficial effects result from phospholipid membrane remodeling, impairment of inflammatory signaling molecules clustering, subsequent inhibition of NF-κB and inflammasome activation, and a reduction in oxidative stress. Obesity, a chronic inflammatory disease that contributes to metabolic disorders, is alleviated by n-3 PUFAs. In the adipose tissue (AT) of individuals with obesity, n-3 PUFAs counteract hypoxia, inhibit immune cell infiltration and AT inflammation, improve insulin sensitivity, and reduce fat mass. Beyond AT, n-3 PUFAs also alleviate other metabolic disorders such as metabolic-associated steatotic liver disease (MASLD), gut dysbiosis, and/or renal dysfunction. In cardiovascular disease (CVD), they are mainly recommended as a secondary prevention for patients with coronary heart disease risks. This review provides an in-depth analysis of the benefits of n-3 PUFAs in obesity and related metabolic diseases, examining both the mechanistic and clinical aspects. Additionally, it also explores the effects of n-3 PUFAs in obesity-related chronic inflammatory conditions, including inflammatory bowel disease, psoriasis, rheumatoid arthritis, osteoarthritis, and multiple sclerosis, by targeting specific pathophysiological mechanisms. Clinical applications and limitations of n-3 PUFAs are discussed based on findings from human clinical trials.
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DOI: 10.3390/nu17071253
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