Anti-obesity effects of Ishophloroglucin A from the brown seaweed Ishige okamurae (Yendo) via regulation of leptin signal in ob/ob mice

Abstract

Brown seaweeds, which are macroalgae, are common foods and traditional medicines for Asians. Ishige okamurae (Yendo), found in Korea's shallow coastal areas, is one of the edible and medicinal brown seaweeds. Recent studies verified the pharmacological activities of the valuable properties from brown seaweeds such as ishophloroglucin A, a phlorotannin from I. okamurae. Recently, many studies have presented the anti-obesity effects of brown seaweeds and their secondary metabolites, such as phlorotannins. However, studies that target the appetite hormone leptin are few. In this study, we explored the natural anti-obesity agents from brown seaweeds targeting leptin. Also, we investigated the anti-obesity effects of ishophloroglucin A, using in vivo and in vitro experiments. The prospective anti-obesity agents were explored in silico among diverse phlorotannins from brown seaweeds. The anti-obesity effects of ishophloroglucin A (2.5 mg/kg, oral administration for seven weeks) were evaluated in ob/ob mice, serving as a leptin-deficiency model. To verify the leptin signal regulation efficacy of ishophloroglucin A, the key molecules of leptin signal were measured in the leptin receptor-silenced N1 hypothalamic neuron cell line using immunocytochemistry. According to the in silico simulation, ishophloroglucin A favorably docks with the leptin receptor. In in vivo results, ishophloroglucin A treatment reduced body weight, fat mass, and food intake. The leptin signaling in the hypothalamus and the insulin signaling in peripheral organs were stimulated by ishophloroglucin A treatment. Moreover, in leptin receptor-silenced N1 cells, ishophloroglucin A treatment failed to induce the leptin signals, unlike in general N1 cells. These scientific results present that ishophloroglucin A from I. okamurae possesses the anti-obesity effect through the leptin signaling pathway and suggest that ishophloroglucin A can be used as sustainable and natural therapeutic ingredients to reduce obesity in leptin-deficient individuals.