A novel therapeutic strategy of obesity from the perspective of SPMs

The global prevalence of obesity and type 2 diabetes mellitus (T2DM)—the most common metabolic disorders—has reached epidemic proportions over the past half-century, with obesity being a key driver of insulin resistance and T2DM development. These disorders are characterized by metaflammation (chronic low-grade inflammation across multiple metabolic organs like adipose tissue, liver, muscle, and the gut), which disrupts metabolic homeostasis, exacerbates insulin resistance, impairs insulin secretion, and links to other comorbidities such as cardiovascular diseases. A major advance in understanding inflammation resolution is the identification of specialized pro-resolving mediators (SPMs), a family of lipid mediators including resolvins, lipoxins, protectins, and maresins. Derived from polyunsaturated fatty acids (e.g., EPA, DHA), SPMs actively regulate inflammation resolution by constraining pro-inflammatory cell infiltration (e.g., neutrophils), promoting anti-inflammatory macrophage polarization (M2), enhancing efferocytosis (clearance of apoptotic cells), and preserving tissue barrier integrity—without inducing immunosuppression. This review summarizes evidence from human and animal studies on obesity-related metaflammation in metabolic tissues and the role of SPMs in resolving this inflammation. It details SPM mechanisms (e.g., maintaining adipose tissue homeostasis, improving insulin sensitivity, alleviating hepatic steatosis) and highlights their dysregulation in obesity (e.g., impaired biosynthesis, reduced receptor expression) as a critical driver of metabolic dysfunction. Finally, the review discusses the therapeutic potential of SPM-targeted strategies (e.g., ω-3 PUFA supplementation, SPM receptor activation) for alleviating obesity, T2DM, metabolic dysfunction-associated steatotic liver disease (MAFLD), and other metabolic disorders, along with future research directions in this field.