Abstract
Background: Korean red ginseng marc (KRGM), a by-product of Korean red ginseng (KRG) processing, retains numerous bioactive compounds with potential health benefits. Among them, KRGM-derived gintonin (KRGM-gintonin) is particularly rich in lysophosphatidic acid (LPA) and phospholipids, which have been linked to favorable metabolic effects. This study investigated the anti-obesity potential of KRGM-gintonin in high-fat diet (HFD)-induced obese mice, focusing on its impact on weight regulation, liver health, and energy metabolism. Methods: Obese mice (C57BL/6N, 4 weeks, male) were administered KRGM-gintonin either orally for 25 weeks or through intracerebroventricular (ICV) injection for 14 weeks. Throughout the study, body weight, food intake, metabolic parameters, liver tissue morphology, behavioral performance, and thermogenic gene expression were carefully monitored to evaluate treatment effects. Results: Both oral and ICV administration of KRGM-gintonin significantly reduced body weight gain in HFD-fed obese mice without altering food intake, suggesting enhanced energy expenditure. Treatment through both routes improved physical performance and increased metabolic rate. Oral KRGM-gintonin also alleviated fatty liver, reduced plasma triacylglycerol and cholesterol levels, and promoted the expression of thermogenesis-related genes, including uncoupling protein-1 (UCP1) and hormone-sensitive lipase (HSL), specifically in brown adipose tissue. Additionally, oral administration lowered tumor necrosis factor-α (TNF-α) expression, indicating anti-inflammatory activity and further supporting metabolic health. Conclusions: KRGM-gintonin exerts strong anti-obesity effects, primarily through oral administration, with supportive evidence from central ICV action. These findings highlight its potential as a functional therapeutic agent for obesity prevention and management, offering dual benefits in metabolic regulation and inflammation control.