Objective:

To evaluate the effects of 5-tetradecyloxy-2-furoic acid (TOFA) on body weight, fat mass, and metabolic parameters in preclinical models of obesity.

Approach:

• Primary Experiment: Male C57BL/6 J mice were fed a high-fat diet and treated with TOFA or vehicle for 4 weeks.
• Metabolic-Cage Experiments: Mice with diet-induced obesity were monitored for changes in fat mass and energy expenditure.
• Histologic Assessments: Liver health and metabolic markers were evaluated in mice treated with TOFA.
• Combination Therapy: TOFA was assessed in combination with incretin-based treatments for weight loss and metabolic control.

Key Findings:

• TOFA treatment resulted in an average 18% decrease in body weight without changing food intake.
• Weight reduction was primarily due to fat-mass loss, with no significant change in lean mass.
• TOFA improved fasting blood glucose, insulin levels, glucose tolerance, and insulin sensitivity.
• Energy expenditure increased by approximately 18% in TOFA-treated mice compared to controls.
• Histologic assessments showed reductions in hepatic steatosis, inflammation, and fibrosis.
• TOFA treatment also reduced liver and serum triglycerides and cholesterol.

Limitations:

• All experiments were conducted on male mice; efficacy and safety in female models are not assessed.
• The minimum efficacious dose for weight loss is undetermined.
• The safety profile at the doses used was incompletely characterized for subclinical toxicity.

Sources:

• Science Advances