A total of 71 studies underwent eligibility assessment, and 55 studies were excluded for various reasons, such as being single-arm studies, observational studies, studies not evaluating the gene expression of PPAR-γ, α or serum levels of FGF-21, studies not conducted in patients with metabolic diseases or insulin impairment (obesity, diabetes, dyslipidemia, polycystic ovary syndrome, and heart disease), and studies using a combination of omega-3 fatty acids with other nutrients or bioactive agents. The gene discussed is FGF21; the disease is obesity due to melanocortin 4 receptor deficiency.