Transcutaneous allicin oleogel restores energy homeostasis for obesity treatment.

Allicin, a bioactive compound derived from garlic, exhibits therapeutic potential against metabolic disorders but is hindered by instability and a pungent odor, limiting its clinical application. This study develops an allicin oleogel (OG) formulation, leveraging molecular interactions with unsaturated fatty acids and gelators to stabilize allicin and mitigate its odor for transcutaneous delivery. The skin analysis confirmed superior transdermal delivery and accumulation in subcutaneous fat with OG, highlighting its advantages for topical application. In a high-fat diet (HFD)-induced mouse model of obesity, OG demonstrated superior efficacy in suppressing weight gain, reducing food intake, and improving metabolic parameters, including fasting blood glucose, oral glucose tolerance, and insulin sensitivity, compared to orally administered allicin oleogel (OGO) and metformin (MET). OG also ameliorated non-alcoholic fatty liver disease (NAFLD), as evidenced by reduced hepatic lipid accumulation and normalized adipose tissue metabolism. Notably, OG treatment shifted macrophage polarization toward an anti-inflammatory M2 phenotype and increased mitochondrial activity, facilitating adipose tissue remodeling and enhancing energy expenditure and thermogenesis. Safety evaluations revealed no systemic toxicity, supporting its potential for long-term use. This study underscores transcutaneously delivered OG as a promising therapeutic strategy for obesity and related metabolic disorders.