Abstract
Obesity, marked by excessive fat accumulation, especially abdominal, is a global health concern with significant public impact. While obesity-associated chronic unresolved inflammation contributes to metabolic dysfunctions, acute inflammation supports healthy adipose tissue remodeling and expansion. Platelet-activating factor (PAF), a "primitive" signaling molecule, is among the key mediators involved in the acute phase of inflammation and in various pathophysiological processes. This article explores the role of PAF in fat accumulation and obesity by reviewing experimental data from cell cultures, animals, and humans. It proposes an emerging biochemical mechanism in an attempt to explain its dual role in the healthy and obese adipose tissue, including also data on PAF's potential involvement in epigenetic mechanisms that may be linked to the "obesity memory". Finally, it highlights the potential of natural PAF modulators in promoting functional adipose tissue, thermogenesis, and obesity prevention through a healthy lifestyle, including a Mediterranean diet rich in PAF weak agonists/PAF receptor antagonists and regular exercise, which help maintain controlled PAF levels. Conversely, in cases of obesity-related systemic inflammation with excessive PAF levels, potent PAF inhibitors like ginkgolide B and rupatadine may help mitigate metabolic dysfunctions with PAFR antagonists potentially enhancing their effects synergistically.