Beneficial Effects of Omega-3 Fatty Acids on Obesity and Related Metabolic and Chronic Inflammatory Diseases

Abstract

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.

Keywords: Th17 cells; chronic metabolic diseases; inflammation; inflammatory bowel disease; multiple sclerosis; obesity; omega-3 polyunsaturated fatty acids; psoriasis; rheumatoid arthritis.

Figure 1

Metabolism of n-3 PUFAs. Conversion of ALA into EPA and DHA metabolites and EPA and DHA into resolvins, maresins, and protectins. Abbreviations: HEPE: hydroxyperoxyeicosapentaenoic acid; HDHA: hydroxyperoxydocosahexaenoic acid.

Figure 2

Biological effects of n-3 PUFAs on chronic inflammatory diseases related to obesity. Obesity exacerbates several chronic inflammatory immune diseases due to its low-grade inflammatory state. n-3 PUFAs contribute to the resolution of such inflammatory diseases though multiple pathways. Up and down arrows correspond to enhancing or inhibiting effects, respectively.