Liposomal formulation co-encapsulating α-tocopheryl succinate and α-tocopherol ameliorates high-fat diet-induced...

Area of Science:

• Biochemistry
• Pharmacology
• Metabolic Diseases

Background:

• Lipid accumulation inhibition is crucial for developing anti-obesity drugs.
• α-Tocopheryl succinate (TS), a derivative of α-tocopherol (T), shows potential for inhibiting lipid accumulation but exhibits cytotoxicity.
• TS-induced cytotoxicity is linked to reactive oxygen species production, which can be counteracted by α-tocopherol (T).

Purpose of the Study:

• To evaluate the efficacy and safety of a liposomal formulation co-encapsulating α-tocopheryl succinate (TS) and α-tocopherol (T) (TS/T-lipo) for obesity treatment.
• To investigate the in vitro effects of TS/T-lipo on cytotoxicity and lipid accumulation.
• To assess the in vivo effects of TS/T-lipo on a high-fat diet-induced obese mouse model.

Main Methods:

• Preparation and in vitro evaluation of TS/T-lipo for cytotoxicity and lipid accumulation inhibition.
• Assessment of Uncoupling Protein 1 (UCP1) expression.
• In vivo study using a high-fat diet-induced obese mouse model to measure body weight, liver toxicity, blood glucose, and serum glycerol levels.
• Histological analysis of adipose tissue.

Main Results:

• TS/T-lipo demonstrated significant inhibition of lipid accumulation in vitro without inducing cytotoxicity.
• Lipid accumulation inhibition in vitro may be mediated by the upregulation of Uncoupling Protein 1 (UCP1), promoting lipid consumption.
• In vivo studies showed a significant decrease in body weight in the TS/T-lipo treated group without adverse effects on liver toxicity or blood glucose levels.
• Increased serum glycerol levels suggest enhanced lipolysis, and histological analysis confirmed reduced lipid accumulation.

Conclusions:

• Co-administration of α-tocopheryl succinate (TS) and α-tocopherol (T) within a liposomal formulation (TS/T-lipo) effectively reduces obesity.
• TS/T-lipo mitigates the cytotoxicity associated with TS, presenting a safer and promising therapeutic candidate for anti-obesity interventions.
• The mechanism involves inhibiting lipid accumulation potentially through UCP1 upregulation and promoting lipolysis.